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.

Pericardial injury by antibacterial irrigants.

We injected antibacterial solutions into rabbit pericardium to investigate tissue injury. Povidone-iodine was the only irrigant found to cause substantial damage. These data lend experimental support to recent clinical observations that suggest a causal relation between pericardial irrigation with povidone-iodine and the later development of constrictive pericarditis.

Systemic thromboembolism from a ventricular septal patch.

The occurrence, diagnosis and treatment of the unreported complication of systemic thromboembolism from a ventricular septal defect patch is described.

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)

Trends and results in tricuspid valve surgery.

Forty-six tricuspid valve operations were performed over 12 years. Operations were conservative (two valvotomies, eight DeVega annuloplasties, seven Carpentier rings) in 17 and valve replacement (17 mechanicals, 12 tissues) in 29. Operative mortality rate was improved with better preoperative functional class, use of cardioplegia, or use of annuloplasty. Heart block occurred less with annuloplasty (6 vs 24 percent). Long-term survival was similar with annuloplasty or porcine valve replacement, but was poorer with mechanical valve replacement. Four of eight DeVega annuloplasties failed during the operative (two) or late (two) period. When the anatomy is suitable, we believe the Carpentier ring annuloplasty to be safe and effective. When valve replacement cannot be avoided, we believe replacement with a tissue valve is preferable.

A comparison of endoesophageal tubes. Improved results with the Atkinson tube.

We reviewed our use of endoesophageal tubes for the palliation of patients with carcinoma of the esophagus from 1973 through 1986. Celestin tubes were implanted by means of laparotomy and traction. Proctor-Livingston tubes were implanted by pulsion with frequent laparotomy for staging. All Atkinson tubes were placed by means of the pulsion method without simultaneous laparotomy in any case. Patients with an Atkinson tube had fewer complications, including aspiration, sepsis, reflux, and pneumonia. Mean hospital stay was shortened to 4 days when the Atkinson tube was used, and hospital death rate was 6% versus 42% when either the Celestin or Proctor-Livingston tube was used. Mean long-term survival (108 days) was significantly lengthened when Atkinson tubes were used. A comparison of all patients receiving tubes revealed a less frequent prevalence of reflux when the distal end of the tube was positioned above the gastroesophageal junction. Laparotomy resulted in significantly more episodes of aspiration, sepsis, reflux, and pneumonia. Laparotomy was also associated with a 41% hospital death rate versus 17% when laparotomy was not performed. Hospital days were shortened to 7 versus 16 days when laparotomy was not performed. The Atkinson tube provided improved palliation and decreased morbidity and mortality in our hands. These benefits were probably the results of ease of insertion without the use of a laparotomy and the ability in most cases to position the distal end of the tube above the gastroesophageal junction.

Chemotherapy, radiation therapy, and resection for carcinoma of the esophagus. Long-term results.

From May 1980 to May 1984, preoperative chemotherapy (mitomycin C and 5-fluorouracil) was added to radiation therapy in patients with potentially operable squamous cell carcinoma of the esophagus. Of 129 patients observed, 122 were followed up until death or to the present. Only 33 were able to complete preoperative chemotherapy and radiation and undergo resection. There were 28 men and five women, their ages ranging from 42 to 81 years (average 60 years). There were 22 black and 11 white patients. The location of the tumor was in the middle third in 70% of the patients. Among the 33 patients, the clinical TNM classification was as follows: T1 N0 M0, three patients; T2 N0 M0, 27 patients; T2 N1 M0, two patients; and T3 N0 M0, one patient. The length of the lesions when measurable in the absence of complete obstruction varied from 3 to 17 cm (average 7 cm). The operative mortality rate in this group was 12% (4/33). There was no viable residual tumor in the surgical specimen of the esophagus in 33% (11/33) of those patients completing triple therapy. However, in two of the 11 patients, left gastric nodes contained tumor and in one there was a minute esophageal perforation. The 2-year survival rate was 33% (11/33), and the 5-year survival rate was 15.4% (5/33). Among the 11 patients having 2-year survival, the surgical specimen was normal in six and abnormal in five. Of the five patients having 5-year survival, the surgical specimen was normal in three and abnormal in two. The absence of tumor in the surgical specimen did not appear to confer any better chance for long-term survival. Data were compared to our 1967-1975 series of 75 patients receiving only preoperative radiation and resection. There was no significant difference in survival rates at 2 years (20% [1975] versus 33% [1984], p = 0.2118) or at 5 years (10% [1975] versus 15.4% [1984], p = 0.5796). The addition of preoperative chemotherapy as an adjunct did not result in a statistically significant increase in 2-year or 5-year survival rates.

A prospective randomized study of hydroxyethyl starch, albumin, and lactated Ringer's solution as priming fluid for cardiopulmonary bypass.

The ideal priming fluid for cardiopulmonary bypass is not known. We designed a study to determine whether there are important differences in the clinical effects of hydroxyethyl starch versus albumin when used in priming fluid, and in the clinical effects of colloid versus crystalloid priming fluid. We prospectively randomized 83 adult patients undergoing coronary artery bypass or valve replacement. All patients were managed by standardized protocol, and they received one of three priming fluids for bypass: hydroxyethyl starch (HES), 26 patients; albumin (ALB), 28 patients, and lactated Ringer's solution (LRS), 29 patients. The groups were stratified by body weight and type of operation. We measured 41 variables relating to operative time factors, fluid balance, bleeding, and organ function (renal, cardiac, and pulmonary) at several time intervals. The LRS group had a significantly lower colloid osmotic pressure than the other two groups, and the HES group had a substantially higher blood viscosity. Although the prothrombin time was significantly lower in the LRS group (p less than 0.05), the differences were very small and not clinically important. The platelet count in the HES group was significantly lower than in the other two groups immediately after bypass, but it was not different by the time the patients left the operating room. There were no differences among the groups in chest tube drainage, blood bank usage, or fluid balance. Postoperatively, the pulmonary shunt fraction was significantly greater in the LRS group. Body weight increased more in the LRS than in the HES and ALB groups (p = 0.01). No adverse reaction to the prime solutions was noted. The differences between the HES and ALB groups--prothrombin time, platelet count, and blood viscosity--had no apparent clinical effects; thus, the two may be considered clinically equivalent. The greater somatic and pulmonary fluid accumulation in the LRS group suggests that colloid is preferable to crystalloid in priming fluid.

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.

Forceps extraction of permanent pacing leads.

With the advent of tined transvenous cardiac pacing leads, the complete extraction of pacing leads in the treatment of an infected cardiac pacing system has become increasingly difficult. A method is described for the extraction of permanent pacing leads from the heart using alligator forceps inserted transvenously through the right internal jugular vein, grasping the lead near its insertion point in the cardiac muscle.

Superior vena cava bypass: use of the azygos vein.

Unexpected involvement of the superior vena cava with dense inflammatory and fibrous tissue was encountered during right pneumonectomy for a T3 N0 M0 squamous cell carcinoma. After expeditiously completing the lung resection, the azygos vein was utilized for a successful superior vena cava bypass.

St. Jude prosthesis for aortic and mitral valve replacement: a ten-year experience.

From January 1, 1979 through December 1990, 456 adult patients underwent isolated aortic (AVR) (254) or mitral (MVR) (202) valve replacement with the St. Jude prosthesis at the Medical University of South Carolina. Age ranged from 21 to 84 years (mean: 54 +/- 15 years for AVR; 51 +/- 13 years for MVR). Male sex predominated in the AVR group (66%) and female sex in the MVR group (64%). Ninety-two patients (20%) had associated coronary artery bypass grafting (AVR, 25%; MVR, 14%). There were 17 deaths (3.7%) occurring during the same hospitalization or within 30 days (AVR, 10/254 [3.9%]; MVR, 7/202 [3.5%]). Follow-up is 94.5% complete and ranges from 1.0 to 131 months (mean, 55 +/- 37 months; total, 2,073 patient-years). In the AVR group, 53 late deaths have occurred and actuarial survival is 80% +/- 3% at 5 years and 47% +/- 9% at 10 years. Twenty-one patients have sustained thromboembolic episodes (1.8%/patient-year), and the probability of remaining free of thromboembolism at 10 years is 67% +/- 13%. The mean improvement in New York Heart Association functional class from preoperative to postoperative is 3.1 +/- 0.76 to 1.6 +/- 0.84 (p < 0.0001). In the MVR group, there have been 41 late deaths, and the actuarial survival was 80% +/- 3% at 5 years and 63% +/- 5% at 10 years. Twenty-eight patients have sustained thromboembolic complications (2.9%/patient-year), and the probability of remaining free of thromboembolism at 10 years is 77% +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Cardiac pacing under hyperbaric conditions.

Temporary external pacemakers have been reported to fail under hyperbaric conditions. In this study we investigated cardiac pacing under hyperbaric conditions. Permanent hermetically sealed pacemakers were found to function well under hyperbaric conditions, while several models of temporary external pacemakers failed. The electrical characteristics of pacing leads did not change under hyperbaric conditions. External pacing under hyperbaric conditions may be accomplished safely by using a permanent pacemaker attached to the patient's temporary external leads.

Prospective, randomized trial of palliative treatment for unresectable cancer of the esophagus.

To evaluate the best method of palliation for obstructing nonresectable squamous cell carcinoma of the mid or distal esophagus, 27 patients were prospectively randomized to one of three treatment arms: (1) esophageal intubation with an Atkinson tube (AT, 10 patients), (2) esophageal intubation followed by radiation therapy (AT/RT, 8 patients), and (3) endoscopic laser therapy followed by irradiation (L/RT, 9 patients). Pretreatment characteristics were similar in the three groups. There was no procedure-related mortality. There were eight total complications related to the tube and none related to laser treatment (p = 0.02). Mean survival was 119 days in the AT group, 72 days in the AT/RT group, and 169 days in the L/RT arm (p = not significant). Quality of survival was most dependent on swallowing ability, and the swallowing score increased by 2.3 units in the AT group, 1.8 units in the AT/RT group, and 1.4 units in the L/RT group (p = not significant). Adding RT to laser therapy significantly increased time in treatment (mean, 38.7 days) when compared with the AT group (mean, 12.5 days) (p less than 0.001). However, only 1 patient required repeat laser ablation. It is concluded that AT and L/RT result in good palliation as measured by relief of dysphagia and survival time. However, morbidity of AT is significantly greater than that of L/RT. Laser and radiation therapy with a reduced total dosage of RT or with a change in fractionation schedule to limit treatment time is the preferred method of palliation.

Atrioventricular pacing in congenital heart disease.

We have attempted to optimize cardiac performance in patients with congenital heart disease requiring artificial pacing by using pacemakers capable of both sensing and pacing both the atrium and the ventricle (DDD). We reviewed our results with 88 patients receiving DDD devices to determine the safety and dependability of these devices in children. Age ranged from 1 hour to 25 years. Endocardial leads were used in 68 patients, whereas epicardial leads were used in 20 patients. Previous cardiac procedures had been done in 30 patients. There were nine deaths but none due to pacemaker malfunction. Endocardial leads functioned better than epicardial leads. Ninety-eight percent of patients with endocardial leads and 62% of patients with epicardial leads were maintained in the DDD mode. Complications were infrequent and all were corrected without long-term sequelae. The DDD mode may offer considerable benefits to children who require artificial pacing. Our data allow us to conclude that most children can be paced safely and dependably in the DDD mode.

Comparison of three blood-processing techniques during and after cardiopulmonary bypass.

The return of extracorporeal circuit blood at the termination of cardiopulmonary bypass is an important feature of blood conservation during open heart procedures. However, the relative benefits and disadvantages of different circuit blood salvage methods remain unclear. Accordingly, the purpose of this study was to examine whether quantifiable differences exist between three different circuit blood-salvaging techniques: direct infusion, centrifugation, and ultrafiltration. Sixty patients with very similar preoperative characteristics were randomly assigned to each of the three groups, and blood coagulation screens, plasma profiles, and respiratory function were determined at 20 minutes and at 6 and 18 hours after cardiopulmonary bypass. Early after cardiopulmonary bypass (20 minutes), the plasma colloid osmotic pressure and fibrinogen and platelet concentrations were significantly higher with ultrafiltration (p < 0.05) versus those observed for the other two methods. The plasma thromboplastin times were significantly (p < 0.05) longer after cardiopulmonary bypass with centrifugation as compared to direct infusion and ultrafiltration. However, the coagulation profiles and plasma composition normalized by 18 hours after cardiopulmonary bypass with all three blood-salvaging methods. There were no significant differences in terms of blood utilization or chest tube drainage over the entire postoperative period among any of the circuit blood-salvaging methods. These results suggest that ultrafiltration of postcardiopulmonary circuit blood may preserve plasma colloid pressure and platelet concentration in the early postoperative period, but these differences do not persist. Thus, for routine cardiopulmonary bypass procedures, direct infusion, centrifugation, and ultrafiltration may all be satisfactory methods of circuit blood salvage.

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.

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.

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.