Strychnos pseudoquina A. St. Hil.: a Brazilian medicinal plant with promising in vitro antiherpes activity.

AIMS: To investigate the anti-HSV and anti-inflammatory effects of a standardized ethyl acetate extract (SEAE) prepared with the stem bark of Strychnos pseudoquina, along with two isolated compounds: quercetin 3-O-methyl ether (3MQ) and strychnobiflavone (SBF). METHODS AND RESULTS: The mechanisms of action were evaluated by different methodological strategies. SEAE and SBF affected the early stages of viral infection and reduced HSV-1 protein expression. Both flavonoids elicited a concentration-dependent inhibition of monocyte chemoattractant protein-1 (MCP-1), whereas 3MQ reduced the chemokine release more significantly than SBF. Conversely, both compounds stimulated the production of the cytokines TNF-α and IL-1-ß in LPS-stimulated cells, especially at the intermediate and the highest tested concentrations. CONCLUSIONS: SEAE and SBF interfered with various steps of HSV replication cycle, mainly adsorption, postadsorption and penetration, as well as with ß and γ viral proteins expression; moreover, a direct inactivation of viral particles was observed. Besides, both flavonoids inhibited MCP-1 selectively, a feature that may be beneficial for the development of new anti-HSV agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicated that the samples present anti-HSV and anti-inflammatory activities, at different levels, which is an interesting feature since cold and genital sores are accompanied by an inflammation process.

An HPLC-UV method for the measurement of permeability of marker drugs in the Caco-2 cell assay

The Caco-2 cell line has been used as a model to predict the in vitro permeability of the human intestinal barrier. The predictive potential of the assay relies on an appropriate in-house validation of the method. The objective of the present study was to develop a single HPLC-UV method for the identification and quantitation of marker drugs and to determine the suitability of the Caco-2 cell permeability assay. A simple chromatographic method was developed for the simultaneous determination of both passively (propranolol, carbamazepine, acyclovir, and hydrochlorothiazide) and actively transported drugs (vinblastine and verapamil). Separation was achieved on a C18 column with step-gradient elution (acetonitrile and aqueous solution of ammonium acetate, pH 3.0) at a flow rate of 1.0 mL/min and UV detection at 275 nm during the total run time of 35 min. The method was validated and found to be specific, linear, precise, and accurate. This chromatographic system can be readily used on a routine basis and its utilization can be extended to other permeability models. The results obtained in the Caco-2 bi-directional transport experiments confirmed the validity of the assay, given that high and low permeability profiles were identified, and P-glycoprotein functionality was established.

An HPLC-UV method for the measurement of permeability of marker drugs in the Caco-2 cell assay.

The Caco-2 cell line has been used as a model to predict the in vitro permeability of the human intestinal barrier. The predictive potential of the assay relies on an appropriate in-house validation of the method. The objective of the present study was to develop a single HPLC-UV method for the identification and quantitation of marker drugs and to determine the suitability of the Caco-2 cell permeability assay. A simple chromatographic method was developed for the simultaneous determination of both passively (propranolol, carbamazepine, acyclovir, and hydrochlorothiazide) and actively transported drugs (vinblastine and verapamil). Separation was achieved on a C18 column with step-gradient elution (acetonitrile and aqueous solution of ammonium acetate, pH 3.0) at a flow rate of 1.0 mL/min and UV detection at 275 nm during the total run time of 35 min. The method was validated and found to be specific, linear, precise, and accurate. This chromatographic system can be readily used on a routine basis and its utilization can be extended to other permeability models. The results obtained in the Caco-2 bi-directional transport experiments confirmed the validity of the assay, given that high and low permeability profiles were identified, and P-glycoprotein functionality was established.

Use of autologous radial artery for revascularization of hepatic artery thrombosis after orthotopic liver transplantation: case report and review of indications and options for urgent hepatic artery reconstruction.

Hepatic artery thrombosis (HAT) is the most common vascular complication after orthotopic liver transplantation (OLT) and has traditionally been managed with re-OLT. However, several reports have shown that urgent revascularization is frequently an effective means of graft salvage. This most often involves hepatic artery (HA) thrombectomy and thrombolysis, with reestablishment of arterial inflow through a donor iliac artery conduit based on the supraceliac or infrarenal aorta. We report a 46-year-old man who developed HAT 13 days after OLT after angiographic splenic artery embolization to reduce splenic artery steal. A suitable donor iliac artery was not available for arterial reconstruction and could not be obtained from neighboring transplant centers. The patient underwent urgent HA thrombectomy, intrahepatic arterial thrombolysis, and revascularization using an autologous radial artery (RA) conduit based on the supraceliac aorta. The patient is alive more than 1 year after revascularization, with normal liver function and documented flow in the arterial conduit by Doppler ultrasound and arteriography. He has not developed late biliary complications or adverse sequelae of RA harvest. Autologous RA can be safely and successfully used as an aortic-based arterial conduit in urgent revascularization of HAT after OLT. RA should be considered for use in HA revascularization if an adequate donor iliac artery is not available and other potential conduits are not usable or desirable. The availability of autologous RA expands the armamentarium of vascular conduits that can be used in HA revascularization and may help minimize re-OLT for otherwise potentially salvageable liver allografts.

Endothelin-1 during and after cardiopulmonary bypass: association to graft sensitivity and postoperative recovery.

OBJECTIVE: Our objectives are 2-fold: (1) to serially measure the release of endothelin and graft-conduit endothelin sensitivity during and after coronary artery bypass grafting and (2) to define potential relationships of changes in endothelin levels to perioperative parameters. METHODS: Endothelin plasma content was measured in patients (n = 105) undergoing bypass grafting from select vascular compartments before operations and at specific intervals up to 24 hours postoperatively. Endothelin sensitivity was determined in isolated internal thoracic artery segments. RESULTS: Systemic arterial and pulmonary arterial endothelin levels were increased by approximately 50% immediately after bypass grafting and increased by another 85% during the first 24 hours postoperatively. Endothelin levels were highest in patients with prolonged ventilatory requirements and extended stays in the intensive care unit (10.2 +/- 0.8 vs 13.2 +/- 1.1 fmol/mL, P =.02, and 9.8 +/- 0.7 vs 13.9 +/- 1.2 fmol/mL, P =.01, respectively. Endothelin sensitivity of the internal thoracic artery was increased in patients requiring prolonged vasodilator support with nitroglycerin. CONCLUSIONS: Systemic and pulmonary arterial endothelin levels remained increased for at least 24 hours postoperatively. Prolonged pharmacologic management and increased intensive care unit stay were associated with increased systemic endothelin release and heightened graft-conduit sensitivity to endothelin.

Coronary artery bypass grafting with and without cardiopulmonary bypass: a comparison analysis.

Coronary artery bypass grafting (CABG) using stabilization devices in place of the heart-lung machine is being performed on a wide range of patients. This study retrospectively compared the performance of off-pump coronary artery grafting bypass (OPCAB) with conventional bypass patients over the same 6-month period at The Medical University of South Carolina. Data were collected and compared from the National Cardiac Database of the Society of Thoracic Surgeons (STS). Parameters studied included age, gender, left ventricular ejection fraction (LVEF), previous myocardial infarction (MI), disease severity, number of grafts, complications, blood usage, ventilation times, operating room (OR) time, and hospital length of stay (LOS). There were no significant difference between the patient groups with regard to age, gender, LVEF, previous MI, predicted mortality, and LOS. Operative mortality was also similar in the two groups: conventional bypass 4/117 (3%) and OPCAB 2/86 (2%). The conventional bypass patients (CPB) had significantly (p < 0.05) more diseased vessels (2.9 vs. 2.6) and distal grafts (4.1 vs. 2.7), as compared to the OPCAB group. OPCAB procedures resulted in significantly (p < 0.05) lower mean OR time (365 min vs. 406 min) and reduced mean postoperative ventilation hours (3.4 vs. 8.3 hours), as compared to conventional bypass. There were significantly (p < 0.05) fewer blood transfusions in the OPCAB group (1.1 units vs. 2.4 units), and the percentage of patients transfused blood was significantly less (34.9% vs. 57.3%). Nine out of 95 (9.5%) of patients who presented for OPCAB were converted to conventional bypass. Although there may be potential benefits to OPCAB, further studies must be directed at determining those patients who would benefit most from CABG using the off-pump technique.

Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases.

BACKGROUND: A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown. METHODS: Systemic plasma MMP levels were measured in patients (n = 28, 63 +/- 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay. RESULTS: The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis. CONCLUSIONS: A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery.

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.

Early and long-term results of coronary artery bypass grafting in dialysis patients.

BACKGROUND: Dialysis patients frequently present with debilitating coronary artery disease but are regarded as challenging patients for coronary artery bypass grafting. METHODS: The operative, early postoperative, and late results of 44 dialysis patients undergoing coronary artery bypass grafting from 1984 to 1997 were retrospectively reviewed. RESULTS: Compared with patients in The Society of Thoracic Surgeons database who underwent coronary artery bypass grafting, only cerebrovascular accident and postoperative cardiac arrest occurred more frequently in dialysis patients. However, 73% experienced some type of complication. Operative mortality was 11.4%. Decreased left ventricular ejection fraction and severe distal disease were predictive of increased operative mortality. New York Heart Association angina class fell from 2.8 to 1.5, and New York Heart Association congestive heart failure class fell from 2.6 to 1.8. Overall quality-of-life scores did not improve; however, walking distances remained consistently improved. Actuarial survival at 5 years was 32.0%+/-12.0%. Five-year survival was 0% for smokers and 83.6%+/-7.6% for nonsmokers (p = 0.0142). Causes of late death were myocardial infarction (4), sepsis (1), subdural hematoma (1), stroke (1), and unknown (6). CONCLUSIONS: Coronary artery bypass grafting should be avoided in dialysis patients with severe diffuse disease. A smoking history is associated with poor outcome. Coronary artery bypass grafting in dialysis patients is associated with a higher incidence of complications but can be performed with an acceptable operative mortality and is associated with good symptomatic relief of angina and heart failure.

Differential effects of calcium channel antagonists in the amelioration of radial artery vasospasm.

BACKGROUND: Radial artery (RA) is being used for coronary artery bypass grafting (CABG) with greater frequency. However, RA is prone to post-CABG vasospasm, which may be neurohormonally mediated. Use of the calcium channel antagonist diltiazem has been advocated as a strategy to reduce post-CABG RA vasospasm. However, whether and to what degree different calcium channel antagonists influence neurohormonally induced RA vasoconstriction remains unknown. METHODS: RA segments were collected from patients undergoing elective CABG (n = 13), and isometric tension was examined in the presence of endothelin (10 nM) or norepinephrine (1 microM). In matched RA, endothelin- or norepinephrine-induced contractions were measured in the presence of diltiazem (277 nM), amlodipine (73 nM), or nifedipine (145 nM). These concentrations of calcium channel antagonists were based upon clinical plasma profiles. RESULTS: Endothelin and norepinephrine caused a significant increase in RA-developed tension (0.54+/-0.1 and 0.68+/-0.1 g/mg, respectively; p<0.05). Amlodipine or nifedipine significantly reduced RA vasoconstriction in the presence of endothelin (30+/-6% and 41+/-9%, respectively; p<0.05) or norepinephrine (27+/-8% and 53+/-9%, respectively; p<0.05), whereas diltiazem did not significantly reduce RA vasoconstriction. CONCLUSIONS: These results demonstrate that neurohormonal factors released post-CABG can cause RA vasoconstriction, and that calcium channel antagonists are not equally effective in abrogating that response. Both amlodipine and nifedipine, which have a higher degree of vascular selectivity, appear to be the most effective in reducing RA vasoconstriction.

Long-term experience with the St. Jude Medical valve prosthesis.

BACKGROUND: All patients undergoing St. Jude Medical valve replacement at the Medical University of South Carolina since January 1979 have been followed prospectively at 12-month intervals. METHODS: This report describes long-term experience in 710 adult patients undergoing isolated aortic (AVR) (418) or mitral valve replacements (MVR) (292) with this prosthesis from January 1979 to December 1996. RESULTS: Ages ranged from 19 to 84 years (54.8 +/- 15.1 AVR, 51.8 +/- 12.9 MVR; mean +/- SD). Male gender predominated in the AVR group (70%) and female gender in the MVR group (62%). One hundred and fifty-seven patients (22%) had associated coronary artery bypass grafting (AVR 27%, MVR 15%). Thirty-day operative mortality was 5.3% (22/418) in the AVR group and 5.1% (15/292) in the MVR group. Follow-up is 96.9% complete and ranges from 1 month to 16.9 years (AVR, 2,376 patient-years, mean 5.7 +/- 4.5 years; MVR, 1,868 patient-years, mean 6.4 +/- 4.8 years). In the AVR group, 120 late deaths have occurred and actuarial survival was 78.0 +/- 2.3%, 58.0 +/- 3.2%, and 36.8 +/- 4.8%; at 5, 10, and 15 years, respectively. Forty-six patients have sustained 55 thromboembolic (TE) events (2.3%/patient-year). Fifty-one patients had anticoagulant-related bleeding complications (2.7%/patient-year). The mean improvement in New York Heart Association (NYHA) functional class from preoperative to postoperative was 3.0 +/- 0.8 to 1.7 +/- 0.1 (p < 0.05). In the MVR group, there have been 84 late deaths, and the actuarial survival was 79.3 +/- 2.5%, 60.1 +/- 3.5%, and 49.3 +/- 4.1% at 5, 10, and 15 years, respectively. Fifty-two patients have had 64 TE events (3.5%/patient-year). Twenty-three patients had anticoagulant-related bleeding complications (1.6%/patient-year). The mean improvement in NYHA functional class was from 3.3 +/- 0.6 to 1.8 +/- 0.1. There were no mechanical failures in either group. CONCLUSIONS: With a follow-up now extending to 17 years, the St. Jude Medical valve continues to be a reliable mechanical prosthesis with low and stable rates of valve-related complications.

Current concepts in heart valve surgery.

After a period of relatively regimented approaches for mitral and aortic valve surgery, recent years have seen numerous innovations including improved prostheses, improved techniques for repair, better understanding of the physiology of ventricular function and myocardial protection, advances in anticoagulation control, and most recently the application of minimally invasive techniques. Each of these has contributed to the improved short and long term results obtained from valve surgery, and further evolution of these techniques will undoubtedly improve the results even more. As operative risks are decreased and long term results are improved, it is hoped that patients with valvular heart disease will be referred at progressively earlier stages of their disease for consideration for surgery. Earlier referral increases the likelihood that valve repair will be possible in the case of the mitral valve and also increases the odds that the outcome from valve surgery will be successful for both aortic and mitral valves.

Fate of gelatin-resorcinol-formaldehyde/glutaraldeyde adhesive on femoral vessel morphology.

Several clinical reports have demonstrated that gelatin-resorcinol-formaldehyde/glutaraldehyde (GRFG) glue can be useful in the repair of acute aortic dissection; however, the cellular and extracellular events that follow GRFG application, as well as the mechanisms responsible for the long-term strength and adhesive properties of GRFG, remain unclear. Accordingly, the present study examined the long-term effects of GRFG adhesive application on femoral vessel extracellular structure and composition. The left and right femoral artery and vein were sterilely exposed in adult rats, and GRFG (2 mL) was applied between and around one pair of vessels. An equivalent amount of sterile saline was applied to the contralateral vessels to serve as an intrinsic control. At either 1 (n = 6) or 2 (n = 6) months postoperatively, the lower extremities were perfusion fixed and harvested to preserve the native anatomy and cytoarchitecture of the femoral region. Gross examination of the specimens revealed no evidence of necrosis or wound breakdown. Tissue blocks (4 microm) were then sectioned perpendicular to the treated vessel region and subjected to histomorphometric analysis using computer-assisted microscopy. The perivascular capsule area, relative content of fibrillar collagen, and number of nucleated cells within the interstitial space were computed. At 1 and 2 months following the application of GRFG adhesive, perivascular capsular size increased by 42 and 221%, respectively. Perivascular interstitial collagen content increased by 21% at 1 month and by 50% at 2 months. The nucleated cell number increased by 107% at 1 month and by 166% at 2 months. This cellular infiltrate appeared to be of fibroblastic morphology. Thus, a potential contributory mechanism to the long-term strength and adhesive capacities of GRFG adhesive may be extracellular remodeling and not the intrinsic properties of GRFG glue itself.

Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo.

UNLABELLED: Perioperative bleeding following coronary artery bypass grafting (CABG) is associated with increased blood product usage. Although aprotonin is effective in reducing perioperative blood loss, excessive cost prohibits routine utilization. Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive antifibrinolytic agents, which, when given prophylactically, may reduce blood loss. The present study was undertaken to compare the efficacy of TA and EACA in reducing perioperative blood loss. METHODS: The study population consisted of first-time CABG patients. Patients were allocated in a prospective double-blind fashion: (1) group EACA (loading dose 15 mg/kg, continuous infusion 10 mg/kg per hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of normal saline for 6 hours, N = 19). RESULTS: Treatment groups were similar preoperatively. No significant difference in intraoperative blood loss or perioperative use of blood products was noted. D-dimer concentration was elevated in the control group compared to the EACA and TA groups (p < 0.05). Group TA had less postoperative blood loss than the EACA and control groups at 6 and 12 hours postoperatively (p < 0.05). TA had reduced total blood loss (600 +/- 49 mL) postoperatively compared to EACA (961 +/- 148 mL) and control (1060 +/- 127 mL, p < 0.05). CONCLUSION: TA and EACA effectively inhibited fibrinolytic activity intraoperatively and throughout the first 24 hours postoperatively. TA was more effective in reducing blood loss postoperatively following CABG. This suggests that TA may be beneficial as an effective and inexpensive antifibrinolytic in first-time CABG patients.

Intravenous sedation for placement of automatic implantable cardioverter-defibrillators.

OBJECTIVE: To evaluate a change in anesthetic technique for transvenous placement of the automatic implantable cardioverter-defibrillator (ICD). DESIGN: Retrospective study. SETTING: A university hospital. PARTICIPANTS: Twenty-eight patients who underwent placement of ICDs. INTERVENTIONS: Thirteen patients had the ICD placed via the transvenous approach with general anesthesia (group GA). Fifteen patients had the ICD placed via the transvenous approach with intravenous sedation (group IV). MEASUREMENTS AND MAIN RESULTS: Intraoperative systolic and diastolic blood pressures were significantly higher in group IV compared with group GA. The ICD was successfully placed in all patients in both groups. There were no intraoperative complications noted in either group during induction of fibrillation and defibrillation, and there was no recall by any patient in either group. The average hospital stay was significantly less in group IV (1.8 days) compared with group GA (3.4 days). CONCLUSIONS: Intravenous sedation for the placement of ICDs is a safe and effective technique. Patients who had their ICD placed while receiving intravenous sedation experienced higher intraoperative blood pressures and were discharged from the hospital earlier than those patients who received general anesthesia.

Pseudo fracture of a defibrillating lead.

Routine follow-up chest X ray of several patients with the Endotak transvenous pacing lead suggested fracture of the conductor at the distal end of the proximal defibrillating coil. Electrical evaluation of these patients' leads demonstrated them to be working normally. Multiple x-ray views of a new undamaged lead demonstrated that in some projection the Endotak lead may appear fractured in spite of normal continuity of the conductors. Physicians dealing with these patients should be aware of this confusing x-ray finding.

The risk of small St. Jude aortic valve prostheses.

We reviewed our 12-year experience with 254 adult patients who had St. Jude valves in the aortic position and used multivariate analysis to examine risk factors possibly affecting long-term morbidity and mortality. Nineteen-millimeter or 21-mm valves were implanted in 115 patients. Poor preoperative congestive heart failure status was associated with persistent congestive heart failure on late follow-up. Preoperative congestive heart failure and coronary artery disease were the only predictors of overall late death. Late deaths associated with heart failure and late sudden deaths were examined separately. Preoperative degree of heart failure was the only predictor of late death with associated heart failure. The implantation of a 19- or 21-mm valve in patients with a body surface area greater than 1.9 m2 somewhat increased the risk of late sudden death. In patients with a body surface area greater than 1.9 m2 and with a 19-mm or 21-mm annulus, consideration should be given to using a high-performance St. Jude valve or performing an annulus-enlarging procedure if this can be done with negligible morbidity.

The relation between latissimus dorsi skeletal muscle structure and contractile function after cardiomyoplasty.

Past reports suggest that structural changes within the latissimus dorsi muscle occur with chronic electrical stimulation during cardiomyoplasty. However, the specific changes in the structure of the latissimus dorsi muscle and the relation to muscle contractile function with cardiomyoplasty are unknown. Accordingly, this study examined regional changes in latissimus dorsi muscle structure and function after cardiomyoplasty. The left latissimus dorsi muscle was mobilized and wrapped around the heart in pigs with the use of standardized techniques and the latissimus dorsi muscle chronically paced at ambient heart rates (90 beats/min; 20 Hz, 5 V amplitude, n = 6). After 6 weeks, the paced latissimus dorsi muscle and the contralateral control muscle were removed and divided into proximal (0 to 3 cm), middle (3 to 6 cm), and distal (6 to 12 cm) regions. By computer-assisted morphometry, muscle cell myofibril volume, cross-sectional area, and collagen percent area were determined. In the paced latissimus dorsi muscle, myofibril volumes increased by more than 50% in the proximal and middle regions compared with those in the contralateral control muscle. However, myofibril volumes were significantly lower in the distal region of the paced latissimus dorsi muscle compared with those in control muscles (33% +/- 5% versus 20% +/- 3%, p < 0.05). In the paced latissimus dorsi muscle, cross-sectional area was significantly reduced from that of control muscles in all regions. A further reduction in cross-sectional area was noted in the distal region of the paced latissimus dorsi muscle compared with that in both the contralateral control muscle and the proximal and middle regions of the paced latissimus dorsi muscle. Collagen content significantly increased in the paced latissimus dorsi muscle compared with that in control muscle with a more fibrotic pattern observed in the distal region. Latissimus dorsi muscle strips (less than 2 mm2 cross-sectional area) were harvested, and peak and velocity of tension development were examined after field electrical stimulation at 0.2 to 1.2 Hz. At 0.2 Hz, the velocity of tension development was unchanged in the paced latissimus dorsi muscle compared with that in control muscle. However, peak tension development degraded by only 28% in the paced latissimus dorsi muscles but fell by 51% in control muscles with increased stimulation frequencies. In summary, the contractile function of the chronically stimulated latissimus dorsi muscle was associated with fatigue resistance and increased contractile protein content. However, more distal regions of the paced latissimus dorsi muscle demonstrated atrophy and fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)