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D A Taylor

Publications and source records attributed to D A Taylor.

At least 19 recordsLinked to original sources
PubMed2001

Unifying perspectives of the mechanisms underlying the development of tolerance and physical dependence to opioids.

The cellular basis of tolerance to, and dependence upon, many types of drugs, including opioids, has long defied identification. Tolerance to opioids cannot be explained solely on the basis of modification of opioid receptors or altered metabolism or disposition of the opioid. The development of tolerance following chronic exposure to opioids presents at least three different types of change in cellular responsiveness, each of which has been suggested to represent some type of adaptive modification in cellular responsiveness. These different forms of tolerance are distinguishable on the basis of their time course and whether or not the tolerance is specific for opioid receptor agonists (homologous) or extends to agonists of other systems (heterologous). The adaptive modulation of responsiveness via regulation of cellular proteins has been proposed to be the basis for both longer-term forms of tolerance. The divergent signaling pathways activated by G-protein-coupled receptors like the mu-opioid receptor provide multiple downstream targets for both short- and long-term regulation of cell function that is associated with the development of tolerance and/or dependence. Since the magnitude of receptor activation is an important determinant of the degree to which various signaling pathways are activated, the expressed characteristics of tolerance and/or dependence may be functionally related to which of these diverse pathways are stimulated to the greatest degree. Thus, the possibility that different signaling events are activated either sequentially or concurrently offers the possibility to explain the interaction between these different forms of tolerance and/or dependence.

Animals↗
PubMed2000

Quantification of the alpha(3) subunit of the Na(+)/K(+)-ATPase in developing rat cerebellum.

Cerebellar Purkinje neurons of rats have been shown to exhibit a progressive increase in resting membrane potential as the animals develop postnatally. The magnitude of this increase was equivalent in magnitude to the increase in the depolarizing action of ouabain, consistent with a role for the Na(+)/K(+)-pump in the hyperpolarization. Ouabain binding sites in whole cerebellum also increased with age. The present study was undertaken to confirm that the increases in ouabain binding and the electrophysiological responses to ouabain were a consequence of increases in the sodium pump and to determine whether the changes seen at the whole organ level were reflective of changes taking place at the cellular level. Using antibodies directed against the alpha(1), alpha(2), and alpha(3) subunits of the Na(+)/K(+)-ATPase, rats between 13 and 19 days of age exhibited a statistically significant increase in the relative amount of the alpha(3) subunit at the level of the whole organ, as determined by Western and slot blot analyses, with no change in the levels of either the alpha(1) or the alpha(2) subunit. Using immunohistochemistry, the alpha(3) subunit was shown to increase in both the Purkinje cell layer and the white matter during this postnatal time period, while the alpha(1) subunit increased in the granular layer. These results support and extend previous work, which pointed to a role for the electrogenic sodium pump in the developmental increase in Purkinje cell membrane potential. Furthermore, the data provide a cellular mechanism underlying the increase in resting membrane potential, that is, by the specific modulation of the alpha(3) subunit isoform.

Animals↗
PubMed2000

Developmental changes in metabotropic glutamate receptor-mediated calcium homeostasis.

Neurons of the chick cochlear nucleus, nucleus magnocellularis (NM), require eighth nerve activation of metabotropic glutamate receptors (mGluRs) for maintenance of intracellular calcium homeostasis. Interrupting this activation results in an increase in intracellular calcium concentration ([Ca(2+)](i)) followed by cell atrophy, degeneration, and death of many neurons. Although these phenomena are well characterized in late embryonic and posthatch chicks, little is known about the role of mGluRs and calcium homeostasis during the development of synaptic activity in NM. Using Fura-2 imaging, fluorescent immunohistochemistry, and Western immunoblotting, we investigated (1) the expression and function of group I mGluRs and their role in calcium regulation during development of NM, and (2) the expression of two other key molecules involved in regulating neuronal [Ca(2+)](i) : inositol trisphosphate receptors (IP(3)Rs) and sarcoplasmic/endoplasmic reticulum calcium ATPases (SERCAs). Confocal imaging of Fluo-3-labeled NM was used to investigate the kinetics of global NM neuron calcium signals. Measurements were made at four ages that extend from before synaptic function begins in NM, through functional onset, to mature patterns of spontaneous activity, namely, embryonic days (E) 10, 13, 15, and 18. mGluR5, mGluR1, and SERCA expression peaked at E13 and then decreased with age. IP(3)R expression increased to peak at E18. [Ca(2+)](i) response to mGluR activation increased with age. The rise time of [Ca(2+)](i) signals in NM neurons did not change with development, but E13 neurons were slower to reestablish baseline [Ca(2+)](i). These results suggest that the mGluR-mediated calcium homeostasis of NM neurons develops in parallel with synaptic activity and appears to be refined with increasing synaptic activity.

Aging↗
PubMed2000

Involvement of 5-HT(3) receptors in the nucleus accumbens in the potentiation of cocaine-induced behaviours in the rat.

1. The present study investigated the central effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the role of 5-hydroxytryptamine(3) (5-HT(3)) receptors in the core of the nucleus accumbens (NAc) on cocaine-induced behavioural changes in rats. 2. The 5-HT(3) receptor antagonist ondansetron (1 or 10 ng) was microinjected bilaterally into the core of the NAc 60 min prior to peripheral cocaine (15 mg kg(-1), i.p.) administration followed by the assessment of locomotor activity, rearing activity and head bobs. Both doses of ondansetron attenuated cocaine's stimulatory effect on behaviours. 3. Fluoxetine (0.05 or 5 microg) microinjected bilaterally into the core of the NAc 30 min before peripheral administration of cocaine produced dose-dependent biphasic effects on cocaine-induced behaviours. Intra-NAc administration of 0.05 microg fluoxetine resulted in a potentiation of cocaine-induced behaviours, while the higher dose of the SSRI (5 microg) attenuated the stimulant effect of cocaine on behaviours. 4. To investigate a possible involvement of 5-HT(3) receptors in fluoxetine's facilitatory action, ondansetron (10 ng) was microinjected 30 min prior to fluoxetine (0.05 microg), which resulted in a significant attenuation of the facilitatory effect of fluoxetine on cocaine-induced behaviours. 5. Thus, 5-HT(3) receptors in the core of the NAc appear to mediate stimulatory effects on cocaine-induced locomotor activity, rears and head bobs, whereas the attenuation of cocaine-induced behaviours by fluoxetine at the higher dose, suggests the involvement of a different 5-HT receptor subtype.

Animals↗
PubMed2000

Comparison of incremental and bolus dose inhaled allergen challenge in asthmatic patients.

BACKGROUND: Attenuation of airway responses to inhaled allergen is increasingly used to evaluate anti-asthma drugs. Many studies use different allergen challenge methods and the presence of the late asthmatic response can be identified by a screening challenge with inhalation of incremental doses of allergen. Once defined, subsequent challenges are often administered as a constant dose based on the dose from the screening challenge. Previously, constant dose challenges have been employed but never validated. OBJECTIVE: A comparative study of two methods of delivering inhaled allergen by evaluating the responses of an incremental dose allergen challenge and the same cumulative dose administered as a bolus over a single inhalation. METHODS: Thirty-five male patients with mild allergic asthma underwent incremental dose challenge followed 3-6 weeks later by a bolus dose challenge. Bronchoconstrictor responses were expressed as the maximum percentage fall in FEV1 from baseline during the early (0-2 h) and late (4-10 h) asthmatic responses and area under the percentage change in FEV1-time curve (AUC). RESULTS: There were no significant differences between the challenges. The mean +/- SEM fall in FEV1 following incremental and bolus dose challenge was 33.1 +/- 1.8% and 29.9 +/- 2.2% during the early response, and 36.9 +/- 2.4% and 34.0 +/- 3.1% during the late response, respectively. The mean +/- SEM AUC following incremental and bolus dose challenge was 35 +/- 3 and 33 +/- 3 Delta%FEV1/h for the AUC0-2 h, 147 +/- 12 and 139 +/- 16 Delta%FEV1/h for the AUC4-10 h, and 204 +/- 14 and 190 +/- 19 Delta%FEV1/h for the AUC0-10 h, respectively. CONCLUSION: Bolus dose allergen challenge is a safe method to administer inhaled allergen in clinical trials with a valid response when compared with incremental dose allergen challenge.

Administration, Inhalation↗
PubMed2000

Effects of half ironman competition on the development of late potentials.

OBJECTIVES: The primary purpose was to evaluate the prevalence of late potentials (LPs) in triathletes before and after a half ironman triathlon. The secondary purpose was to examine whether LPs are the electrocardiographic expression of a greater myocardial mass. METHODS: Nine asymptomatic male triathletes (mean age +/- SD, 32 +/- 5 yr) were examined using signal-averaged ECG (SAECG) 48-72 h before (PRE), immediately after (POST), and 24-48 h after the completion (RECOVERY) of a half ironman triathlon. Late potentials were considered to be present if two of the following SAECG anomalies were observed: 1) a prolonged filtered QRS (/QRS) complex (> or = 114 ms), 2) a lengthened low amplitude signal (LAS) duration (>38 ms), and/or 3) a low root mean square (RMS) voltage of the last 40 ms of the fQRS (<20 microV). Left ventricular dimensions were determined at PRE using M-mode echocardiography. RESULTS: There were no significant differences between PRE, POST, and RECOVERY in the fQRS duration, the LAS duration, or the RMS voltage. Two athletes displayed a single SAECG abnormality during PRE and two SAECG anomalies (i.e., LPs) during POST. Late potentials remained in one of the two athletes during RECOVERY. A moderate relationship existed between fQRS and left ventricular mass (r = 0.67, P < 0.05). CONCLUSIONS: Ultra-endurance training and/or events do not lead to LPs in the majority of triathletes who do not possess ventricular arrhythmias. However, a small subset of triathletes do display SAECG anomalies, which are augmented by an ultra-endurance event and may persist even after recovery from the event. Left ventricular mass does not affect overall SAECG parameters.

Adult↗
PubMed2000

Fiber type-specific differential expression of angiogenic factors in response to chronic hindlimb ischemia.

Alterations in endogenous levels of the angiogenic proteins basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were assessed in rabbit hindlimb muscles subjected to 1, 5, or 21 days of ischemia. In the glycolytic [tibialis anterior (TA)] and the oxidative [soleus (SOL)] muscles from the ischemic and contralateral (control) hindlimb, bFGF and VEGF protein expression was determined by ELISA and immunoblot analysis. Total VEGF protein expression was greater in oxidative than in glycolytic muscles after 5 days of hindlimb ischemia. In SOL muscle, total VEGF detected by ELISA in ischemic limbs was increased to 137, 300, and 220% of control at 1, 5, and 21 days, respectively. However, in TA, total VEGF expression by ELISA was increased only at 1 and 5 days of ischemia to 140 and 134% of control, respectively. By immunoblotting, the expression of the 165-amino acid isoform (VEGF(165)) was initially decreased to 55% of control in ischemic SOL at 1 day but was increased to 250% of control at day 5 and remained at 155% at day 21. In TA, VEGF(165) was increased to 260% of control at 1 day of ischemia but only to 150% of control by day 5. The only significant change in bFGF expression in either the oxidative or glycolytic muscles was a small increase (129% of control) at 21 days in SOL. This study demonstrates that the magnitude and direction of change in VEGF protein expression depend on VEGF subtype, muscle fiber type, and duration of ischemia. These findings suggest that strategies in therapeutic angiogenesis may need to differ depending on muscle fiber type.

Animals↗
PubMed2000

A new crop of concerns: Congress investigates pesticide safety.

A March 2000 report by the General Accounting Office, Pesticides: Improvements Needed to Ensure the Safety of Farmworkers and Their Children, states that much remains unknown about the risks faced by children in agriculture, and that enforcement of pesticide protection standards for farmworkers is patchy and unsystematic. Many cases of farmworkers' pesticide-related illnesses go unreported, leaving health workers with an inadequate basis for tracking patterns and fine-tuning pesticide standards, says the report. In addition, children are known to be more vulnerable to the effects of pesticides, but there is a lack of data regarding children's exposures and the precise effects of pesticides on children's health.

Agriculture↗
PubMed2000

Effects of long term resistance training on left ventricular morphology.

OBJECTIVES: To assess the effects of long term (mean +/- SD 10+/-5 years, range three to 25 years) resistance training on left ventricular (LV) dimensions and mass. METHODS AND RESULTS: The study participants were 21 elite male power-lifters (age 33.4+/-5.9 years) and 10 sedentary male control subjects (age 30.9+/-4.2 years). Two-dimensionally guided transthoracic M-mode echocardiograms were obtained at rest to quantify LV diastolic cavity dimension, posterior wall thickness, ventricular septal wall thickness and LV mass. Long term resistance training was not associated with an alteration in LV diastolic cavity dimension (resistance trained 54. 4+/-4.3 mm versus control 51.8+/-5.6 mm), ventricular septal wall thickness (resistance trained 9.7+/-1.0 mm versus control 10.1+/-0.7 mm), posterior wall thickness (resistance trained 9.6+/-1.5 mm versus control 9.3+/-1.4 mm) or LV mass (resistance trained 200. 3+/-32.5 g versus control 186.5+/-39.6 g). In addition, no resistance-trained athlete was found to have an LV mean wall thickness above clinical normal limits (12 mm or less). CONCLUSION: Contrary to common beliefs, long term resistance training as performed by elite male power-lifters does not alter LV morphology.

Adult↗
PubMed2000

Cardiac tamponade as the first clinical manifestation of metastatic adenocarcinoma of the lung.

A 62-year-old woman presented in the emergency department with new onset of dyspnea and clinical signs of cardiac tamponade. She had a history of cigarette smoking and a family history of adenocarcinoma, pancreatic and breast carcinoma. An emergency two-dimensional echocardiogram confirmed the diagnosis of cardiac tamponade. Therapeutic pericardiocentesis resulted in prompt relief. Cytology confirmed malignant glandular cells, consistent with a metastatic adenocarcinoma. Computerized chest tomography confirmed pulmonary involvement.

Adenocarcinoma↗
PubMed2000

Alterations in neuronal gamma-aminobutyric acid(A) receptor responsiveness in genetic models of seizure susceptibility with different expression patterns.

The genetically epilepsy-prone rat (GEPR) is a unique animal model of seizure predisposition with substrains (i.e., GEPR-NE, GEPR-3, and GEPR-9) that exhibit different seizure patterns in response to the same stimulus. Among many deficits identified in these animals, reduced responses to GABA(A) receptor agonists have been described in several brain regions of the GEPR-9. However, few studies have quantitatively analyzed this difference in responsiveness or have examined and compared the responsiveness of GEPR-3 neurons with the other strains. Using intracellular recording, we determined and compared the responsiveness of Purkinje neurons from GEPR-3 animals with those of control (both Sprague-Dawley and GEPR-NE) and GEPR-9 rats at different developmental ages. In GEPR-9 animals, the EC(50) value for GABA and muscimol was shifted 3-fold to the right, with no reduction in maximum. In contrast, GEPR-3 animals showed a significant reduction in the maximum hyperpolarizing response to only GABA and muscimol with no change in the EC(50) values. Responsiveness to glutamate, aspartate, norepinephrine, and diazepam was unchanged in both strains, indicating that the change in responsiveness was highly selective for GABA(A) receptor agonists. Changes in responsiveness in animals <15 days of age suggests that deficits in GABAergic function exist before the development of seizure susceptibility. In addition, the data are the first to reveal that the GEPR-3 and GEPR-9 exhibit different changes in GABA(A) receptor function and may provide significant insight into the cellular mechanism underlying differences between these two strains.

Age Factors↗
PubMed1999

Postradiation sarcomas: 20 cases and a literature review.

PURPOSE: To analyze 20 cases of postradiation sarcoma (PRS) to determine dose levels at which this condition developed, the pathology of the initial and postradiation tumors, latency period, and outcome; and to review the literature and propose modified criteria for diagnosis. METHODS AND MATERIALS: Patient records were reviewed. Previous radiation fields and isodose charts were reconstructed to determine the dose received in the tissue in which the PRS subsequently developed. RESULTS: There were 16 female patients and 4 male patients. Mean age at the time of initial radiotherapy was 28 years. Mean latency was 14 years, with no difference in latency between the adult and pediatric group (t = 0.45, p = 0.37), but shorter latency in the retinoblastoma than in the nonretinoblastoma patients (t = 3.18, p = 0.003). The outcome was poor; 2 patients were alive and disease-free at 2 and 5 years. The 18 patients who died as a result of PRS had a median survival of 1 year. CONCLUSION: PRSs are rare. Unnecessary radiation must be avoided. Cases should be reported with full details so that risk factors can be ascertained. PRSs usually arise in moderate to higher dose areas. Diagnostic criteria should allow soft tissue tumors and short latency.

Adult↗
PubMed1999

Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaine-induced behaviour in the rat.

The present study examined whether a potentiation of cocaine-induced behaviour in rats following peripheral pretreatment with the 5-hydroxytryptamine (5-HT) biosynthesis inhibitor p-chlorophenylalanine may be due to depletion of 5-HT in the dorsal raphe nucleus and/or median raphe nucleus. Following peripheral pretreatment with p-chlorophenylalanine (100 mg/kg, i.p.) for 3 consecutive days, a potentiation of cocaine-induced locomotor activity and rears was observed. To investigate a possible involvement of serotonergic neurones arising in the midbrain raphe nuclei in the observed potentiation, p-chlorophenylalanine (0.5 microg) was microinjected in either the dorsal raphe nucleus or median raphe nucleus followed by behavioural testing 48 h later. Application of p-chlorophenylalanine in the dorsal raphe nucleus resulted in an enhancement of cocaine-induced locomotor activity and head bobs. In contrast, the stimulant effect of cocaine on behaviour was not altered by microinjection of p-chlorophenylalanine in the median raphe nucleus. Peripheral and central administration of p-chlorophenylalanine did not consistently alter the baseline behaviour of saline-treated animals. Biochemical results indicated only a moderate depletion of 5-HT in the midbrain raphe nuclei following peripheral p-chlorophenylalanine administration. Surprisingly, the central application of p-chlorophenylalanine in the dorsal raphe nucleus and median raphe nucleus did not alter the 5-HT levels in the midbrain raphe nucleus investigated. In addition, peripheral and central administration of p-chlorophenylalanine did not alter the 5-HT levels in the nucleus accumbens. In conclusion, the behavioural results suggest that the potentiation of cocaine-induced behaviour following peripheral p-chlorophenylalanine administration may be attributed to the dorsal raphe nucleus but not the median raphe nucleus suggesting that, serotonergic dorsal raphe nucleus neurones may normally mediate a tonic inhibitory effect on cocaine-induced behaviour. Furthermore, the biochemical data may indicate the existence of neurochemical resistance of the midbrain raphe nuclei to the 5-HT depleting effects of p-chlorophenylalanine.

Animals↗
PubMed1999

The role of the sodium pump in the developmental regulation of membrane electrical properties of cerebellar Purkinje neurons of the rat.

The postnatal development of the rat cerebellum has been well described morphologically and functionally. However, information regarding the electrical characteristics of Purkinje neurons during development is sparse. Using standard intracellular recording, the basic electrical properties of Purkinje neurons in cerebellar slices were compared at different postnatal ages. There was a significant, progressive increase in the resting membrane potential (RMP) of Purkinje neurons with age as well as a small but significant decrease in the cellular input resistance (Rin). The cardiac glycoside, ouabain (1 mM), an inhibitor of the sodium pump, depolarized Purkinje neurons significantly more with age. The magnitude of the increase in depolarizing activity of ouabain was equivalent to the magnitude of the increase in membrane potential. The number of ouabain binding sites was also found to increase with age suggesting an age related increase in the number of sodium pump sites. These results suggest that the predominant cellular mechanism which underlies the increase in membrane potential of Purkinje neurons during development is an increase in the density of Na+, K+ pump sites and in the contribution of the electrogenic sodium pump.

Aging↗
PubMed1999

Cellular cardiomyoplasty improves diastolic properties of injured heart.

BACKGROUND: Acute myocardial infarction leads to loss of functional myocytes and structural integrity that often decreases diastolic compliance and increases resting myocardial segment length (diastolic creep). Successfully engrafting autologous skeletal myoblasts could improve compliance and potentially reverse creep. Thus, we transplanted myoblasts into cryoinjured rabbit heart (n = 15, CRYO) and measured regional diastolic properties in the presence (n = 9, +ENG) or absence (n = 6, -ENG) of engraftment. MATERIALS AND METHODS: Left ventricular (LV) pressures (P) and myocardial segment lengths (SL) were measured in vivo by micromanometry and sonomicrometry after cryoinjury (CRYO) and again 3 weeks following transplantation of myoblasts. Performance was estimated from the relationships between end-diastolic (ED) P and strain (epsilon) or between EDP and EDSL. Compliance was characterized by strain (epsilon(8)) and dynamic stiffness (dP/dL(8)) at 8 mm Hg. Creep was characterized by resting myocardial segment length (EDSL(0)) and static stiffness at 8 mm Hg (m(stat8)). RESULTS: Successful myoblast engraftment was determined via histologic examination. In nine +ENG animals, diastolic properties improved. Regional strain (epsilon(8)) increased (0.06 +/- 0.02 CRYO vs 0.10 +/- 0.04 +ENG; P = 0.0009) while dynamic stiffness (dP/dL(8)) decreased (43 +/- 23 mm Hg/mm CRYO vs 23 +/- 14 mm Hg/mm +ENG; P = 0.009). Static stiffness (m(stat8)) was unaffected (0.78 +/- 0.2 mm Hg/mm CRYO vs 0.72 +/- 0. 1 mm Hg/mm +ENG; P = 0.08), and creep did not occur (EDSL(0) = 10.3 +/- 2.8 CRYO vs 10.4 +/- 2.3 +ENG; P = 0.74). In the absence of myoblast engraftment (n = 6, -ENG), strain decreased (epsilon(8) = 0. 06 +/- 0.02 CRYO vs 0.05 +/- 0.02 -ENG; P = 0.048), but dynamic stiffness (dP/dL(8)) did not (36 +/- 19 mm Hg/mm CRYO vs 28 +/- 12 mm Hg/mm -ENG; P = 0.20). Furthermore, static stiffness decreased (0. 78 +/- 0.3 mm Hg/mm CRYO vs 0.65 +/- 0.2 mm Hg/mm -ENG; P = 0.05) and creep was obvious (EDSL(0) = 10.8 +/- 3.6 mm CRYO vs 13.0 +/- 4. 4 mm -ENG, P = 0.04). CONCLUSIONS: Myoblast engraftment may partially overcome the loss of myocytes and structural integrity that often follow chronic myocardial ischemia. Improved compliance and reversal of diastolic creep suggest regeneration of viable muscle within once infarcted myocardium.

Animals↗
PubMed1999

Modulation of cocaine-induced locomotor activity, rears and head bobs by application of WAY100635 into the dorsal and median raphe nuclei of the rat.

The present study investigated the role of somatodendritic 5-HT1A autoreceptors located in the dorsal and median raphe nuclei on the stimulant effect of cocaine on locomotor activity, rears and head bobs in female Glaxo Wistar rats. Cocaine was administered at a submaximal dose of 15 mg/kg i.p. to enable either a potentiation or attenuation to be observed. The selective 5-HT1A antagonist WAY100635 (0.21 ng or 21 ng) or saline was microinjected in the dorsal or median raphe nuclei followed by the peripheral administration of cocaine 60 min later. WAY 100635 microinjected in the dorsal or median raphe nuclei did not consistently alter the locomotor activity and the number of rears of saline-treated animals. Microinjection of WAY100635 in the dorsal raphe nucleus potentiated cocaine-induced locomotor activity and the number of head bobs. The number of rears induced by cocaine was not significantly altered by WAY100635 microinjected in the dorsal raphe nucleus. In contrast, microinjection of WAY100635 in the median raphe nucleus did not alter the stimulant effect of cocaine on locomotor activity, rears or head bobs. It may be suggested from these results that stimulation of somatodendritic 5-HT1A autoreceptors located in the dorsal raphe nucleus mediates an inhibitory effect on cocaine-induced locomotor activity and head bobs, whereas somatodendritic 5-HT1A autoreceptors in the median raphe nucleus are not involved in the inhibitory role of 5-HT on the stimulant effect of cocaine on locomotor activity and head bobs. A differential involvement of the midbrain raphe nuclei may exist controlling the stimulant effect of cocaine on locomotor activity and head bobs.

Anesthesia↗
PubMed1999

Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ.

BACKGROUND: Adult heart lacks stem cells and cannot effectively regenerate. In contrast, skeletal muscle is constantly undergoing repair. We proposed to transplant immature skeletal myoblasts into injured myocardium. METHODS: Approximately 7x10(6) soleus skeletal myoblasts were expanded in vitro from adult New Zealand White rabbits (n = 23) whose posterior left ventricle was cryoinjured to create a transmural lesion. Autologous myoblasts (n = 18) or saline (n = 5) was transplanted into the central cryolesion at the time of injury (n = 6) or 1 week later (n = 12). Hearts were harvested 2 weeks after injection. RESULTS: Myoblast transfer did not incur further morbidity. After cryolesion, grossly, a 1.6-cm epicardial hemorrhagic lesion could be seen. Histologically, the transmural lesion contained inflammatory cells and active scarring but no viable cardiomyocytes. Electron microscopy demonstrated a predominance of collagen and fibroblasts. Nine hearts contained multinucleated cells within the cryolesion that covered approximately 75% of the central cryolesion in 17% of animals. Immunohistochemical analysis confirmed their skeletal muscle origin. At the periphery of the lesion, isolated clusters of nonskeletal muscle cells could be visualized (n = 12) that resembled immature cardiocytes. CONCLUSIONS: Autologous skeletal myoblasts can regenerate viable striated tissue within damaged myocardium. Myoblast transfer warrants further investigation as a new method for improving myocardial performance within infarcted myocardium.

Animals↗