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Biomedical subjects

W R Chitwood

Publications and source records attributed to W R Chitwood.

At least 19 recordsLinked to original sources

The temporal expression of transforming growth factor-beta 1 in early aortocoronary vein grafts.

The success of coronary reconstructive procedures is limited by the high incidence of restenosis secondary to intimal hyperplasia (IH). Transforming growth factor-beta 1 (TGF-beta 1) is a growth factor which has been shown to be important in the early development of IH in arteries and peripheral vein grafts. To date, there is little information concerning the early remodeling in aortocoronary vein grafts (ACVG). The purpose of this study was to characterize the expression of TGF-beta 1 expression in early aortocoronary vein grafts. Eighteen mongrel dogs underwent aortocoronary vein bypass grafting. Vein grafts were excised at 2 hr, 4 hr, and 7 days after implantation, snap frozen, and processed for ribonuclease protection assays (RPA) using 32P-labeled riboprobes for TGF-beta 1 and 18 S rRNA. TGF-beta 1 expression was quantified by densitometric analysis of autoradiographs which were expressed as a ratio TGF-beta 1/rRNA. Representative vessel rings were also collected for histology. There was a significant rise in TGF-beta 1 expression in the 2-hr vein grafts (0.42 +/- 0.04 compared to control saphenous vein (0.21 +/- 0.05, P < 0.02). In addition, there was significant downregulation of TGF-beta 1 at 4 hr (0.28 +/- 0.05) and at 7 days (0.18 +/- 0.01) when compared to 2 hr (P < 0.05). Histological specimens showed minimal intimal hyperplasia at 7 days. These results show for the first time an acute rise in TGF-beta 1 expression in ACVG. This upregulation quickly subsides by 4 hr and gene expression approaches control values by 7 days. By understanding this temporal relationship of expression one could better target potential therapeutic modalities to attenuate IH.

Animals

Minimally invasive mitral valve repair using transthoracic aortic occlusion.

This report describes a minimally invasive mitral valve repair done through a limited (6-cm) thoracic incision. The patient was supported by peripheral extracorporeal perfusion with cardiac arrest established using a new transthoracic aortic cross-clamp and antegrade blood cardioplegia. The patient was discharged on postoperative day 3 with minimal pain. This less invasive approach to mitral valve surgery may offer combined advantages to patients by increasing comfort, expediting recovery, and decreasing surgical costs by using modified traditional methods compared with specialized intraaortic occlusive balloons.

Cardiac Surgical Procedures

Extracardiac adjustment of mitral chordae replacement.

This study was designed to determine the feasibility of completing mitral chord repair externally when the heart was weaned from bypass. Ten anesthetized dogs (22.9 +/- 4.6 kg) were placed on cardiopulmonary bypass through a left thoracotomy. The left atrium was opened and one or two marginal chords of the anterior mitral leaflet were divided. A double-armed 2-O polypropylene suture was placed in the margin of the mitral leaflet, and both suture ends were brought outside of the ventricle through the anterior papillary muscle, but were not anchored. Production of mitral incompetence was verified when the animals were weaned from bypass. Mean left atrial pressure (LAPm), the v wave of the left atrial pressure (LAPv), systolic billowing of the anterior leaflet into the left atrium above the mitral closure line (two-dimensional echocardiography, long axis), and function curves (left atrial-aortic systolic pressure, LAPv-AoSP) were used to determine valve competence and functionality of the repair. All values are expressed as means +/- SE. Acute mitral incompetence in this model was associated with severe left atrial bulging, left atrial billowing of the anterior leaflet (7-12 mm, 9.6 +/- 1.6 mm), significantly increased left atrial pressure [LAPv, 30.5 +/- 5.8; LAPm, 23.6 +/- 4.3 mm Hg; both P < 0.01 vs control (10.5 +/- 2.5 and 7.5 +/- 2.7 mm Hg, respectively)], and decreased systemic pressure development (AoSP, 84 +/- 8.8 vs 108 +/- 12.3 mm Hg; P < 0.01). The slope of the atrial-systemic pressure curve was decreased significantly, shifted to the right and reduced by more than half (2.1069 vs 0.9190; P < 0.05). External adjustment of the pledgeted suture ends returned all values to within control limits (LAPv, 12.7 +/- 4.1; LAPm, 9.8 +/- 4.3; AoSP, 104 +/- 10.5; LAP-AoSP slope, 2.0909; all P = n.s.), atrial bulging was not evident, and atrial displacement of the valve leaflet could no longer be visualized. These data suggest that mitral chord repair is feasible through a thoracotomy and, more importantly, final adjustments to obtain optimal chord length can be completed externally, guided by changes in dynamic, physiologic parameters.

Animals

Distal flow determinants in canine myocardium perfused through internal thoracic artery bypass grafts.

The dynamic reactivity and the acute, recruitable flow capacity of an internal thoracic artery (ITA) graft remains unclear. These experiments were conducted in 20 anesthetized dogs with the left ITA grafted to the circumflex artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle, including anterior descending artery and circumflex regions, totally dependent on the ITA graft. When the left main coronary artery was occluded, the ITA flow immediately increased more than fivefold (93.4 +/- 9.6 mL/min; mean +/- standard deviation), representing an absolute flow value three times higher than ITA flow measured in situ on the chest wall (27.5 +/- 9.6 mL/min; p < 0.05 versus control), and the ITA graft provided total resting flow requirements (93.4 +/- 9.6 mL/min) for both left anterior descending and circumflex coronary artery perfusion territories at levels comparable with measured native flow values (y = (0.9555)x + 21.9272; r = 0.976; p < 0.05). Pharmacologic challenge with adenosine (0.2 mg.kg-1.min-1 intravenously) significantly increased the graft flow (120.3 +/- 18.7 mL/min; p < 0.05 versus control), but also significantly decreased the mean arterial pressure (85.4 +/- 5.0 versus 74.6 +/- 6.1 mm Hg; p < 0.05). Phenylephrine (0.003 mg.kg-1.min-1 intravenously) significantly decreased ITA graft flow (81.2 +/- 9.0 mL/min; p < 0.05 versus control) despite significantly increased perfusion pressure (84.8 +/- 6.3 versus 108.2 +/- 8.6 mm Hg; p < 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

Complex valve operations: antegrade versus retrograde cardioplegia?

BACKGROUND: Increasingly complex cardiac procedures demand optimal myocardial protective techniques during the requisite interval of aortic cross-clamping. For complex procedures in which prolonged cross-clamp times are anticipated, we favor combined antegrade and retrograde cold blood cardioplegia. Advantages include rapid arrest, uniform distribution, and an uninterrupted operation. METHODS: We retrospectively evaluated the cases of 194 consecutive patients who underwent complex cardiovascular procedures between January 1988 and October 1994. Procedures performed included valve repair and coronary artery bypass grafting (23.7%), valve replacement and coronary artery bypass grafting (19.1%), complex aortic arch and valve procedures (16.6%), valve repair only (16.5%), reoperative valve (9.8%), and multiple-valve replacements (9.3%). Cardioplegic arrest times averaged 113 +/- 38.5 minutes (range, 52 to 292 minutes). RESULTS: Postoperative left and right ventricular function was evaluated using transesophageal echocardiography. The echocardiograms revealed a 3.1% incidence of new left ventricular dysfunction and no case of right ventricular dysfunction. Of the patients evaluated, 75.7% required little (< 3 micrograms.kg-1.min-1 of dopamine hydrochloride) or no inotropic support postoperatively. The 30-day mortality rate was 3.1%, and no death was due to cardiac failure. CONCLUSIONS: We conclude that myocardial protection using a combined antegrade and retrograde cardioplegia technique permits excellent myocardial protection during complex cardiovascular procedures requiring long arrest times.

Adult

Experimental supplemental vein grafting and hypoperfusion syndrome.

An additional saphenous vein graft (SVG) sometimes is required to the same coronary system if acute internal thoracic artery (ITA) graft flow is inadequate. These experiments were conducted to determine the consequences produced by ITA-SVG dual grafting. Fourteen dogs each received two coronary grafts (without bypass, using local occlusion) to the proximal circumflex coronary artery, using the ITA and an SVG, and then the circumflex artery was ligated proximally. Simultaneous flow in both grafts was determined at rest and after pharmacologic (adenosine, phenylephrine) or physiologic (cardiac pacing) stimulation. Serial angiography was performed during the first 4 weeks after grafting to determine patency patterns of the ITAs and SVGs. In the resting heart, flow was 7.5 +/- 1.6 mL/min (17.5%) in the ITA graft and 35.3 +/- 5.2 mL/min (82.5%) in the SVG (mean +/- standard deviation [% total distal perfusion]), and the combined flow was not significantly different from the original native flow. Intravenous adenosine (0.2 mg.kg-1.min-1) preferentially increased both the total ITA flow and its fractional contribution to total distal perfusion (18.4 +/- 3.2 [31.1%]; p < 0.05 versus rest). Saphenous vein graft flow was not changed significantly (40.3 +/- 6.0 mL/min), in part due to a modest decrease in arterial pressure. In contrast, intravenous phenylephrine (0.003 mg.kg-1.min-1) decreased both absolute ITA flow and its relative contribution to distal perfusion (6.1 +/- 1.1 [10.9%]; p < 0.05 versus rest), despite an increased systemic perfusion pressure, which increased SVG flow significantly (50.1 +/- 4.8 [89.1%]; p < 0.05 versus rest).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

Pericardial fluid adenosine in ischemic and valvular heart disease.

Adenosine released by ischemic myocardial cells stimulates coronary artery vasodilation. Measurement of adenosine concentrations in pericardial fluid in animal models of myocardial ischemia has been used to study the process of adenosine release. To determine whether pericardial fluid adenosine concentrations are increased in human ischemic heart disease, adenosine concentrations were measured in pericardial fluid in 23 subjects undergoing open-heart surgery for coronary artery disease. The results were compared with adenosine concentrations measured in pericardial fluid obtained from 20 subjects undergoing surgery for valvular heart disease. Adenosine concentrations also were measured in pleural fluid obtained during internal mammary artery bypass grafting. Adenosine concentrations were significantly increased in subjects with coronary artery disease compared with fluid obtained from subjects with valvular heart disease (2.47 +/- 0.24 vs 1.36 +/- 0.21 [SEM] microM [p = 0.0013]). Adenosine concentrations were higher in pleural fluid than pericardial fluid from the same individuals. Adenosine concentrations were significantly correlated with pericardial fluid cell counts and lactate dehydrogenase concentrations (r = 0.48; p = 0.0012 and r = 0.77, p = 0.0001, respectively). The results are consistent with myocardial release of adenosine in ischemic heart disease. If adenosine concentrations in pericardial fluid approximate those in myocardial interstitial fluid, sufficient adenosine is present to stimulate adenosine receptor activation in coronary artery smooth muscle.

Adenosine

Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model.

The ability of allopurinol to protect against reperfusion injury in the heart has usually been attributed to its xanthine oxidase (XO)-inhibiting properties. Human myocardium however, has exhibited low levels of XO activity. To investigate the effects of allopurinol in an XO-free model and determine whether pretreatment is necessary, 12 domestic pigs (15 kg to 20 kg) underwent occlusion of the left circumflex for 8 minutes followed by reperfusion for 4 hours. One group received allopurinol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control group (n = 6) received a saline infusion (same volume). Left ventricular and aortic pressure, electrocardiograms, and regional wall motion (sonomicrometry) were monitored throughout the process. Regional blood flow (microspheres) were obtained before, during, and 5, 10, and 30 minutes after ischemia. Occlusion decreased transmural flow at the midpapillary level by 75% (0.28 versus 1.10 mL/minute/g). The allopurinol-treated group exhibited a mild, generalized hyperemia at 5 minutes (ischemic zone: 1.44 versus 1.10 mL/min/g, which returned to control levels at 10 and 30 minutes. In contrast, the control group was associated with only 80% restoration of resting blood flow at 5 minutes (0.84 versus 1.10 mL/min/g), which stabilized at 63% of control levels at 10 and 30 minutes. When evaluated for the propensity of arrhythmias using an arbitrary arrhythmia score, the allopurinol group demonstrated no myocardial ectopy when compared with the focal ectopy routinely encountered in the control group at all time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol

Effect of chronic native flow competition on internal thoracic artery grafts.

Residual competitive flow from the native coronary artery has been proposed as a mechanism that reduces flow in an internal thoracic artery graft (ITA), resulting in narrowing and ultimately failure of the graft. Results from acute experiments have indicated that competitive flow from a fully patent native artery did not abolish ITA graft flow. The present study was designed to examine the consequences of dynamic flow competition between the native vessel and the ITA graft in a chronic model. Fifteen mongrel dogs underwent coronary artery bypass grafting using the pedicled left ITA anastomosed to the normal, fully patent circumflex (CFX) coronary artery. The procedure was performed through a sterile thoracotomy, without systemic cardiopulmonary bypass, using a brief local occlusion to construct the anastomosis. Intraoperatively, ITA flow was measured in situ on the chest wall, before the pedicle was mobilized. Internal thoracic artery graft and distal CFX flow were measured after the anastomosis was completed, with and without brief occlusion of the proximal CFX. Angiography was performed 72 hours, 4 weeks, and 8 weeks later; graft patency and diameter were evaluated. After 8 weeks, open-chest direct flow measurements comparable with the intraoperative assessment were obtained. Two grafts (13%) occluded early, the technical result of poor anastomotic construction. In the 13 remaining animals, all grafts were widely patent at all time points. Internal thoracic artery flow in situ averaged 10.9 +/- 7.8 mL/min (mean +/- standard deviation), and was maintained after grafting (11.5 +/- 4.4 mL/min; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Will C. Sealy, MD: the father of arrhythmia surgery--the story of the fisherman with a fast pulse.

The development of clinical electrophysiology and arrhythmia surgery has a long and interesting history. On May 2, 1968, Dr. Will C. Sealy, with the electrophysiologists at Duke University, performed the first successful ablation of a pathway in a patient with Wolff-Parkinson-White syndrome using an epicardial approach. Thereafter, he and his colleagues developed improved endocardial techniques to ensure ablation of even multiple and complex anatomic pathways. From this work the impulse to perform these procedures spread worldwide, and a school of arrhythmia surgeons sprouted. For these and other accomplishments, Dr. Sealy clearly became the Father of Arrhythmia Surgery. The story is told herein.

Arrhythmias, Cardiac

Clinical experience with the implantable cardioverter defibrillator.

The implantable cardioverter defibrillator has played an increasingly greater role in the management of episodes of sudden cardiac-related death related to ventricular tachycardia or ventricular fibrillation. This study reviews the cases of 142 patients who underwent insertion of an implantable cardioverter defibrillator, 104 who received a device alone (group I) and 38 who underwent insertion of the device in combination with other cardiac surgical procedures (group II). The overall operative mortality was 3.5% and this did not differ between the two groups. The complication rate was higher for group II than for group I patients, and consisted primarily of an increased incidence of atrial arrhythmias (53% versus 13%; p < 0.001). Late complications included three device infections requiring removal of the defibrillator. The late mortality did not differ between the two groups and was primarily related to congestive heart failure. Sudden cardiac-related death was an uncommon late event, with an actuarial freedom from sudden cardiac-related death of 98%, 97%, and 87% at 1, 2, and 5 years, respectively. The morbidity and mortality rate are low in association with the insertion of an implantable cardioverter defibrillator, even when this is combined with other cardiac surgical procedures. Its insertion is also associated with a low subsequent rate of sudden cardiac-related death.

Adult

Embolectomy of a Bird's Nest Vena Caval Filter.

In this case report we describe a successful embolectomy of a partially migrated Bird's Nest Caval Filter with attached embolic material. We used transesophageal echocardiography to guide the surgical approach. The patient recovered uneventfully from both the embolectomy and the subsequent pelvic operation.

Echocardiography, Transesophageal

PTCA failure.

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Angioplasty, Balloon, Coronary