Alternative splicing associated with phenotypic plasticity in the bumble bee Bombus terrestris.

Phenotypic plasticity is when one genome can produce more than one phenotype. The caste system found in many social insects is an important example of plasticity. Several studies have examined gene expression in social insect developmental and caste differences. Changes in gene expression, however, are not the only source of phenotypic plasticity. Here, we investigate the role of alternative splicing in the buff-tailed bumble bee Bombus terrestris. We found that 5,458 genes in B. terrestris (40%) express more than one isoform. Larvae have the lowest level of splicing events, followed by adults and then pupae. We found that when an isoform is expressed in a given caste in the larval stage, it tends to be expressed in all castes at the larval stage. The same is true at the pupal stage. However, we see more complicated interactions between the adult castes with reproductive females showing different isoform expression compared to nonreproductive females and male adults showing the most distinct patterns. We found 455 isoform switching genes, that is genes, where one developmental stage, sex or caste uses a specific isoform and another type uses a different isoform. Among genes displaying isoform switching are some involved in the ecdysteriod pathway, an important system in insect behaviour.

Transition in sexual system and sex chromosome evolution in the tadpole shrimp Triops cancriformis.

Transitions in sexual system and reproductive mode may affect the course of sex chromosome evolution, for instance by altering the strength of sexually antagonistic selection. However, there have been few studies of sex chromosomes in systems where such transitions have been documented. The European tadpole shrimp, Triops cancriformis, has undergone a transition from dioecy to androdioecy (a sexual system where hermaphrodites and males coexist), offering an excellent opportunity to test the impact of this transition on the evolution of sex chromosomes. To identify sex-linked markers, to understand mechanisms of sex determination and to investigate differences between sexual systems, we carried out a genome-wide association study using restriction site-associated DNA sequencing (RAD-seq) of 47 males, females and hermaphrodites from one dioecious and one androdioecious population. We analysed 22.9 Gb of paired-end sequences and identified and scored >3000 high coverage novel genomic RAD markers. Presence-absence of markers, single-nucleotide polymorphism association and read depth identified 52 candidate sex-linked markers. We show that sex is genetically determined in T. cancriformis, with a ZW system conserved across dioecious and androdioecious populations and that hermaphrodites have likely evolved from females. We also show that the structure of the sex chromosomes differs strikingly, with a larger sex-linked region in the dioecious population compared with the androdioecious population.

Cardiac output is not a significant source of low frequency mean arterial pressure variability.

Spontaneous mean arterial pressure (MAP) variability may be mainly due to fluctuations in cardiac output (CO) and total peripheral resistance (TPR). While high frequency (HF ∼ 0.25 Hz) oscillations in MAP are ultimately driven by respiration, the source of low frequency (LF ∼ 0.1 Hz) fluctuations has not been fully elucidated. It is known that CO buffers these oscillations, but there is no evidence on its potential role in also generating them. The main goal was to determine whether CO is a source of LF variability in MAP. Six dogs were chronically instrumented to obtain beat-to-beat measurements of CO and MAP while the dogs were fully awake and at rest. A causal dynamic model was identified to relate the fluctuations in CO to MAP. The model was then used to predict the MAP fluctuations from the CO fluctuations. The CO fluctuations were able to predict about 70% of the MAP oscillations in the HF band but showed no predictive value in the LF band. Hence, respiration induces CO fluctuations in the HF band that, in turn, cause MAP oscillations, while TPR fluctuations appear to be the dominant mediator of LF fluctuations of MAP. CO is not a significant source of these oscillations, and it may only be responsible for dampening them, likely through the baroreflex.

Low Y chromosome variation in Saudi-Arabian hamadryas baboons (Papio hamadryas hamadryas).

It is important to characterise the amount of variation on the mammalian Y chromosome in order to assess its potential for use in evolutionary studies. We report very low levels of polymorphism on the Y chromosome of Saudi-Arabian hamadryas baboons, Papio hamadryas hamadryas. We found no segregating sites on the Y, despite sequence analysis of 3 kb noncontiguous intron sequence in 16 males with divergent autosomal microsatellite genotypes, and a further analysis of 1.1 kb intron sequence in 97 males from four populations by SSCP. In addition, we tested seven human-derived Y-linked microsatellites in baboons. Only four of these loci were male-specific and only one was polymorphic in our 97 male sample set. Polymorphism on the Y chromosome of Arabian hamadryas appears to be low compared to other primate species for which data are available (eg humans, chimpanzees and bonobos). Low effective population size (Ne) of paternal genes due to polygyny and female-biased adult sex ratio is a potential reason for low Y chromosome variation in this species. However, low Ne for the Y should be counterbalanced to some extent by the species' atypical pattern of male philopatry and female-biased dispersal. Allelic richness averaged over seven loci was not significantly different between an African and an Arabian population, suggesting that loss of variation during the colonisation of Arabia does not explain low Y variation. Finally, in the absence of nucleotide polymorphism, it is unclear to what extent selection could be responsible for low Y variation in this species.

Male parentage does not vary with colony kin structure in a multiple-queen ant.

Kin selection theory predicts that, in social Hymenoptera, the parentage of males should be determined by within-colony relatedness. We present a model showing that, when sex ratios are split (bimodal) as a function of colony kin structure, the predictions of kin selection theory regarding the occurrence of worker reproduction and policing (prevention of worker reproduction) require modification. To test the predictions of kin selection theory and our model, we estimated using microsatellites the frequency of worker-produced male eggs and adults in the facultatively polygynous (multiple-queen) ant Leptothorax acervorum. Analysis of 210 male eggs and 328 adult males from 13 monogynous (single-queen) and nine polygynous colonies demonstrated that the frequency of worker-produced males was low (2.3-4.6% of all males) and did not differ significantly between colony classes or between eggs and adults. This suggested workers' self-restraint as the cause of infrequent worker reproduction in both colony classes. Such an outcome is not predicted either by comparing relatedness values or by our model. Therefore, it appears that factors other than colony kin structure and sex ratio effects determine the pattern of male parentage in the study population. A likely factor is a colony-level cost of worker reproduction.

Ant workers selfishly bias sex ratios by manipulating female development.

Kin selection theory predicts that social insects should perform selfish manipulations as a function of colony genetic structure. We describe a novel mechanism by which this occurs. First, we use microsatellite analyses to show that, in a population of the ant Leptothorax acervorum, workers' relatedness asymmetry (ratio of relatedness to females and relatedness to males) is significantly higher in monogynous (single-queen) colonies than in polygynous (multiple-queen) colonies. Workers rear mainly queens in monogynous colonies and males in polygynous colonies. Therefore, split sex ratios in this population are correlated with workers' relatedness asymmetry. Together with significant female bias in the population numerical and investment sex ratios, this finding strongly supports kin-selection theory. Second, by determining the primary sex ratio using microsatellite markers to sex eggs, we show that the ratio of male to female eggs is the same in both monogynous and polygynous colonies and equals the overall ratio of haploids (males) to diploids (queens and workers) among adults. In contrast to workers of species with selective destruction of male brood, L. acervorum workers therefore rear eggs randomly with respect to sex and must achieve their favoured sex ratios by selectively biasing the final caste (queen or worker) of developing females.

Computerized controlled-substance surveillance: application involving automated storage and distribution cabinets.

A secondary data-reporting system used to scan the archives of a hospital's automated storage and distribution cabinets (ASDCs) for indications of controlled-substance diversion is described. ASDCs, which allow access to multiple doses of the same medication at one time, use drug count verification to ensure complete audits and disposition tracking. Because an ASDC may interpret inappropriate removal of a medication as a normal transaction, users of ASDCs should have a comprehensive plan for detecting and investigating controlled-substance diversion. Monitoring for and detecting diversion can be difficult and time-consuming, given the limited report-generating features of many ASDCs. Managers at an 800-bed hospital used report-writing software to address these problems. This application interfaces with the hospital's computer system and generates customized reports. The monthly activity recapitulation report lists each user of the ASDCs and gives a summary of all the controlled-substance transactions for those users for the time period specified. The monthly summary report provides the backbone of the surveillance system and identifies situations that require further audit and review. This report provides a summary of each user's activity for a specific medication for the time period specified. The detailed summary report allows for efficient review of specific transactions before there is a decision to conduct a chart review. This report identifies all ASDC controlled-substance transactions associated with a user. A computerized report-generating system identifies instances of inappropriate removal of controlled substances from a hospital's ASDCs.

Assessment of skeletal muscle ventricle tissue blood flow using positron emission tomography.

In this pilot study, we assessed the feasibility of using positron emission tomography (PET) imaging for in vivo measurement of skeletal muscle ventricle (SMV) tissue blood flow. In 4 dogs, with SMVs prepared from their latissimus dorsi muscle, we quantified SMV tissue blood flow by PET and related it to the tissue flow measured by radiolabeled microspheres under similar physiologic conditions. The tissue blood flow was estimated in SMVs wrapped around a mandrel (not in circulation) at rest and during SMV stimulation (30 and 90 contraction-cycles/min). SMV tissue perfusion was heterogeneous, especially during SMV contraction. Furthermore, there was a linear relationship between SMV tissue flows estimated by PET and those measured by microspheres. We conclude that in vivo imaging of SMV is feasible by PET. Quantification of SMV tissue blood flow by PET has promise as a means of assessing changes in blood flow, but further technical progress needs to be made before absolute flows can be reliably measured.

Alteration of humoral and peripheral vascular responses during graded exercise in heart failure.

We hypothesized that performance of exercise during heart failure (HF) would lead to hypoperfusion of active skeletal muscles, causing sympathoactivation at lower workloads and alteration of the normal hemodynamic and hormonal responses. We measured cardiac output, mean aortic and right atrial pressures, hindlimb and renal blood flow (RBF), arterial plasma norepinephrine (NE), plasma renin activity (PRA), and plasma arginine vasopressin (AVP) in seven dogs during graded treadmill exercises and at rest. In control experiments, sympathetic activation at the higher workloads resulted in increased cardiac performance that matched the increased muscle vascular conductance. There were also increases in NE, PRA, and AVP. Renal vascular conductance decreased during exercise, such that RBF remained at resting levels. After control experiments, HF was induced by rapid ventricular pacing, and the exercise protocols were repeated. At rest in HF, cardiac performance was significantly depressed and caused lower mean arterial pressure, despite increased HR. Neurohumoral activation was evidenced by renal and hindlimb vasoconstriction and by elevated NE, PRA, and AVP levels, but it did not increase at the mildest workload. Beyond mild exercise, sympathoactivation increased, accompanied by progressive renal vasoconstriction, a fall in RBF, and very large increases of NE, PRA, and AVP. As exercise intensity increased, peripheral vasoconstriction increased, causing arterial pressure to rise to near normal levels, despite depressed cardiac output. However, combined with redirection of RBF, this did not correct the perfusion deficit to the hindlimbs. We conclude that, in dogs with HF, the elevated sympathetic activity observed at rest is not exacerbated by mild exercise. However, with heavier workloads, sympathoactivation begins at lower workloads and becomes progressively exaggerated at higher workloads, thus altering distribution of blood flow.

Mating frequency and mating system of the polygynous ant, Leptothorax acervorum.

Multiple mating by queens (polyandry) and the occurrence of multiple queens in the same colony (polygyny) alter patterns of relatedness within societies of eusocial insects. This is predicted to influence kin-selected conflicts over reproduction. We investigated the mating system of a facultatively polygynous UK population of the ant Leptothorax acervorum using up to six microsatellite loci. We estimated mating frequency by genotyping 79 dealate (colony) queens and the contents of their sperm receptacles and by detailed genetic analysis of 11 monogynous (single-queen) and nine polygynous colonies. Results indicated that 95% of queens were singly mated and 5% of queens were doubly mated. The corrected population mean mating frequency was 1.06. Parentage analysis of adults and brood in 17 colonies (10 monogynous, 7 polygynous) showed that female offspring attributable to each of 31 queens were full sisters, confirming that queens typically mate once. Inbreeding coefficients, queen-mate relatedness of zero and the low incidence of diploid males provided evidence that L. acervorum sexuals mate entirely or almost entirely at random. Males mated to queens in the same polygynous colony were not related to one another. Our data also confirmed that polygynous colonies contain queens that are related on average and that their workers had a mixed maternity. We conclude that the mating system of L. acervorum involves queens that mate near nests with unrelated males and then seek readoption by those nests, and queens that mate in mating aggregations away from nests, also with unrelated males.

Functional assessment of skeletal muscle ventricles after pumping for up to four years in circulation.

BACKGROUND: The successful treatment of cardiac failure by heart transplantation is severely limited by the shortage of donor organs, and alternative surgical approaches are needed. An experimental approach that holds considerable promise is the skeletal muscle ventricle (SMV), an auxiliary blood pump formed from a pedicled graft of latissimus dorsi muscle and connected to the circulation in a cardiac assist configuration. Adaptive transformation, or conditioning, by electrical stimulation enables the skeletal muscle to perform a significant proportion of cardiac work indefinitely without fatigue. METHODS: In 10 dogs, SMVs were constructed from the latissimus dorsi muscle, lined internally with pericardium, and conditioned by electrical stimulation to induce fatigue resistant properties. The SMVs were connected to the descending thoracic aorta via two 12-mm Gore-Tex conduits and the aorta was ligated between the two grafts. The SMV was stimulated to contract during the diastolic phase of alternate cardiac cycles. The animals were monitored at regular intervals. RESULTS: At initial hemodynamic assessment, SMV contraction augmented mean diastolic blood pressure by 24.6% (from 61 +/- 7 to 76 +/- 9 mm Hg). Presystolic pressure was reduced by 15% (from 60 +/- 8 to 51 +/- 7 mm Hg) after an assisted beat. Four animals died early, 1 from a presumed arrhythmia, and 3 during propranolol-induced hypotension. The other 6 animals survived for 273, 596, 672, 779, 969, 1,081, and 1,510 days. Diastolic augmentation was 27.4% at 1 year (93 +/- 9 vs 73 +/- 6 mm Hg; n = 5), 34.7% at 2 years (85 +/- 6 vs 63 +/- 7 mm Hg; n = 3), 21.2% (89 +/- 10 vs 73 +/- 8 mm Hg; n = 2) at 3 years, and 34.5% (78 vs 58 mm Hg; n = 1) after 4 years in circulation. After 4 years, the isolated SMV was able to maintain a pressure of over 80 mm Hg while ejecting fluid at 20 mL/s. No animal showed evidence of SMV rupture or thromboembolism. CONCLUSIONS: The SMVs in this study provided effective and stable hemodynamic assistance over an extended period of time. There was no evidence that the working pattern imposed on the muscular wall of the SMV compromised its viability. Areas of fibrofatty degeneration were suggestive of early damage that future protocols should seek to minimize.

Heart failure alters the strength and mechanisms of the muscle metaboreflex.

We hypothesized that excessive sympathoactivation observed during strenuous exercise in subjects with heart failure (HF) may result from tonic activation of the muscle metaboreflex (MMR) via hypoperfusion of active skeletal muscle. We studied MMR responses in dogs during treadmill exercise by graded reduction of terminal aortic blood flow (TAQ) before and after induction of HF by rapid ventricular pacing. At a low workload, in both control and HF experiments, large decreases in TAQ were required to elicit the MMR pressor response. During control experiments, this pressor response resulted from increased cardiac output (CO), whereas in HF CO did not increase; thus the pressor response was solely due to peripheral vasoconstriction. In HF, MMR activation also induced higher plasma levels of vasopressin, norepinephrine (NE), and renin. At a higher workload, in control experiments any reduction of TAQ elicited MMR pressor responses. In HF, before any vascular occlusion, TAQ was already below MMR control threshold levels and reductions in TAQ again did not result in higher CO; thus SAP increased via peripheral vasoconstriction. NE rose markedly, indicating intense sympathetic activation. We conclude that in HF, the MMR is likely tonically active at moderate workloads and contributes to the tonic sympathoactivation.

Does gender influence the strength and mechanisms of the muscle metaboreflex during dynamic exercise in dogs?

Ischemia of active skeletal muscle stimulates neuronal afferents within the muscle, which elicits a reflex increase in sympathetic nerve activity, systemic arterial pressure (SAP), and heart rate (HR), termed the muscle metaboreflex. We retrospectively investigated whether gender influences the activation of the muscle metaboreflex and the primary mechanisms used by this reflex, augmentation of cardiac output (CO) and peripheral vasoconstriction, using 15 female and 13 male chronically instrumented dogs exercising on a treadmill (3.2 km/h, 0% grade). Metaboreflex activation was achieved via progressive partial vascular occlusion of the terminal aorta during exercise. In both females and males, hindlimb ischemia elicited similar substantial increases in SAP (56.1 +/- 3.0 and 55.1 +/- 4.2 mmHg, respectively), HR (25.8 +/- 4.8 and 33.9 +/- 2.8 beats/min, respectively), and CO (1.39 +/- 0.3 and 1.64 +/- 0.2 liters, respectively) and a similar substantial decrease in renal vascular conductance (RVC; 42.7 +/- 4.9 and 42.9 +/- 5.3%, respectively). Both groups also demonstrated similar metaboreflex thresholds and sensitivities of SAP, HR, CO, and RVC. We conclude that the strength and mechanisms mediating the metaboreflex responses during dynamic exercise in dogs are not affected by gender.

Power output of pericardium-lined skeletal muscle ventricles, left ventricular apex to aorta configuration: up to eight months in circulation.

OBJECTIVE: The purpose of this experiment was to evaluate the potential for a skeletal muscle ventricle connected to the circulation between the left ventricle and the aorta to provide effective, long-term cardiac assist. METHODS: Skeletal muscle ventricles were constructed from the latissimus muscle in 10 dogs. After conditioning, the skeletal muscle ventricles were connected to the left ventricle and the aorta with 2 valved conduits. The skeletal muscle ventricle was programmed to contract during diastole. RESULTS: At time of implantation, skeletal muscle ventricles stimulated at 33 Hz and in a 1:2 ratio with the heart significantly decreased left ventricular work by 56% (P <.01) and at 50 Hz by 65% (P <.01). At a 1:2 ratio, the power output of the skeletal muscle ventricles was 59% of left ventricular power output at 33 Hz (P <. 01) and 93% at 50 Hz (P <.01). Animals survived 7, 11, 16, 17, 72, 99, 115, 214, and 249 days. Three deaths were directly related to the skeletal muscle ventricle. One animal is alive at 228 days. In the animal that survived 249 days, skeletal muscle ventricle power output at 8 months with a 33 Hz stimulation frequency and a 1:2 contraction ratio was 57% of left ventricular power output and 82% at 50 Hz. At a 1:1 ratio, skeletal muscle ventricle power output was 97% and 173% of the left ventricle at 33 and 50 Hz, respectively. CONCLUSIONS: Left ventricular assist with a skeletal muscle ventricle connected between the left ventricle and the aorta is the most hemodynamically effective configuration we have tested and can maintain significant power output up to 8 months.

Skeletal muscle ventricles, left ventricular apex-to-aorta configuration. 1 to 11 weeks in circulation.

BACKGROUND: Skeletal muscle ventricles (SMVs) have been used in animals in a variety of configurations to provide circulatory assistance. Long-term survival and function have been demonstrated. Our laboratory recently obtained promising short-term hemodynamic data in a left ventricular apex-to-aorta model. METHODS AND RESULTS: SMVs were constructed from the left latissimus dorsi muscle in five adult mongrel dogs. After a 3-week period of vascular delay and 5 to 7 weeks of electrical conditioning, valved conduits were used to connect the left ventricular apex to the SMV and the SMV to the descending aorta. The SMV was then stimulated to contract during cardiac diastole. Initial measurements showed a significant increase in the mean femoral diastolic pressure (62 +/- 6 versus 51 +/- 5 mm Hg, P < .05). There was also a decrease in the left ventricular tension-time index (11.5 +/- 2.5 versus 14.6 +/- 2.1 mm Hg.s, P < .05), indicating a decrease in the work requirement of the left ventricle. During SMV stimulation, the majority of flow (65%) was through the SMV circuit and was associated with reversal of flow in the proximal descending thoracic aorta. The longest-surviving animal survived 76 days, at which time pressure augmentation was still seen (mean femoral diastolic pressure, 63 +/- 0.9 versus 50 +/- 1.2 mm Hg, P < .05). CONCLUSIONS: Survival beyond the acute setting is possible with this model. Diastolic pressure augmentation can be effectively maintained over time.

Pericardium-lined skeletal muscle ventricles: up to two years' in-circulation experience.

BACKGROUND: Skeletal muscle ventricles (SMVs) are autologous pumping chambers constructed from skeletal muscle. Skeletal muscle ventricular rupture and thromboembolism have complicated chronic models of this method of skeletal muscle cardiac assist. METHODS: The SMVs were constructed from the latissimus dorsi muscle in 10 dogs. The inner surface of each SMV was lined with autologous pericardium harvested at the time of SMV construction. After a 3-week period of vascular delay and 6 weeks of electrical conditioning to convert the muscle to a fatigue-resistant state, SMVs were connected to the descending thoracic aorta and stimulated to contract during cardiac diastole. RESULTS: Initial hemodynamics revealed that SMV contraction at 33 Hz increased diastolic pressure 24.7% (60.8 +/- 7.3 mm Hg versus 80.3 +/- 8.8 mm Hg). Skeletal muscle ventricle relaxation decreased presystolic pressure 14.4% (59.9 +/- 7.7 mm Hg versus 51.3 +/- 7.5 mm Hg) and decreased peak systolic pressure 4.1% (90.2 +/- 7.3 mm Hg versus 86.5 +/- 5.8 mm Hg). Hemodynamics were assessed at 1 to 2 weeks, then at 1, 2, 3, and 6 months, and at 6-month intervals thereafter. Hemodynamic performance remained stable for the duration of this study. After 2 years of pumping continuously in circulation, SMV contraction resulted in a 34.8% augmentation of diastolic pressure (63.6 +/- 6.6 mm Hg versus 85.3 +/- 6.4 mm Hg), a 17.2% decrease in presystolic pressure (54.7 +/- 3.73 mm Hg versus 45.3 +/- 4.1 mm Hg), and a 4.2% decrease in peak systolic pressure (95.3 +/- 10.4 mm Hg versus 91.3 +/- 12.3 mm Hg). Three dogs survived to 2 years with the SMVs in circulation. No animal showed evidence of thromboembolism during serial echocardiography or at autopsy and no SMVs ruptured. CONCLUSIONS: These data demonstrate that SMVs can provide effective hemodynamic assist over an extended period without specific complications related to the SMVs.

Skeletal muscle as a myocardial substitute.

During the last several years, there has been intense worldwide interest concerning the use of skeletal muscle as a form of cardiac assistance. For over 10,000 people in the United States diagnosed each year with irreversible heart failure, the 1-year mortality approaches 50%. This comes despite recent advances in medical therapy, heart transplantation, and the artificial heart program. Because of the limitations of these treatments in terms of effectiveness, cost, and availability, we have used a different approach for cardiac augmentation. Skeletal muscle is shaped into the form of a pumping chamber and then used to aid the function of the failing myocardium. Another approach is cardiomyoplasty, where the latissimus dorsi muscle is wrapped around the heart and stimulated to contract in synchrony with the patient's failing myocardium. More than 500 patients have undergone cardiomyoplasty worldwide. These two areas of investigation represent the principle methods for skeletal muscle cardiac assistance.

Skeletal muscle ventricles: frontiers in 1995.

Skeletal muscle ventricles (SMVs) constructed from electrically conditioned latissimus dorsi muscle (LDM) may become an alternative for assisting the failing heart. Left and right heart circulatory assist using SMVs has been performed successfully in both acute and chronic animal models. The configurations used to connect SMVs to the circulation have included a left atrium to aorta bypass, a left ventricle apex to aorta bypass, aortic counterpulsators, a cavopulmonary bypass, and a right ventricle to pulmonary artery bypass. One SMV used as an aortic counterpulsator functioned effectively in the circulation for more than 27 months. Recent application of the pericardium to the SMV as an inner layer and design changes in the connection of the SMV to the circulation have reduced the risk of thrombus formation and SMV rupture. Although several problems have yet to be solved, the goal of the SMV as a permanent circulatory assist device without the limitation of an external power source seems within reach.

Skeletal muscle ventricles in circulation: decreased incidence of rupture.

BACKGROUND: Skeletal muscle ventricles (SMVs) are muscular pumping chambers constructed for cardiac assist. Skeletal muscle ventricles can be connected to the circulation in a variety of configurations for both left and right heart assist; when connected to the aorta and stimulated to contract during diastole, they function in a similar fashion as an intraaortic balloon pump. METHODS: Skeletal muscle ventricles were constructed in 18 dogs using the left latissimus dorsi muscle. In 10 of these dogs (group 1), the inner surface of the SMV was lined with autogenous pericardium obtained at the time of construction of the SMV. For the remaining 8, the SMVs were lined by fibrous tissue that forms in reaction to the synthetic mandrel around which the latissimus muscle is wrapped. After the muscles were electrically conditioned to a fatigue-resistant state, the mandrels were removed from the SMVs and the SMVs were connected to the descending thoracic aorta with a specially constructed base cap and two polytetrafluoroethylene conduits. RESULTS: Initial hemodynamic recordings revealed that the mean diastolic blood pressure increased by 24.7% in group 1 and by 29.8% in group 2. Diastolic augmentation was well maintained over time; augmentation in surviving group 1 animals was 30.0% after 18 months of pumping continuously in circulation. Long-term survival was greater in the dogs whose SMVs were constructed using an inner pericardial lining. At 90 days in circulation, 60% of the dogs in group 1 were alive with functioning SMVs, whereas only 13% of the dogs in group 2 were alive. The incidence of SMV rupture in the fibrouslined SMVs was 63%, whereas the incidence in the pericardial-lined SMVs was 0%. No evidence of thromboembolism occurred in either group. CONCLUSIONS: Lining the inner surface of an SMV with pericardium appears to provide structural integrity, which helps to prevent the complication of SMV rupture in this model of cardiac assist.