A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to matrix remodeling in disease states such as tumor metastases. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to increase MMP expression, and membrane-type MMP or MT1-MMP has been implicated to activate MMPs. The present study examined whether and to what degree EMMPRIN and MT1-MMP were expressed in human left ventricular (LV) myocardium as well as the association with MMP activity and expression in dilated cardiomyopathy (DCM). METHODS AND RESULTS: LV myocardial zymographic MMP activity increased by >2-fold with both nonischemic DCM (n=21) and ischemic DCM (n=16) compared with normal (n=13). LV myocardial abundance of MMP-9 was increased with both forms of DCM. MMP-2 and MMP-3 were increased with nonischemic DCM. MMP-1 levels were decreased with both forms of DCM. EMMPRIN increased by >250% and MT1-MMP increased by >1000% with both forms of DCM. CONCLUSIONS: Increased LV myocardial MMP activity and selective upregulation of MMPs with nonischemic and ischemic forms of DCM occurred. Moreover, a local MMP induction/activation system was identified in isolated normal human LV myocytes that was upregulated with DCM. The control of MMP activation and expression in the failing human LV myocardium represents a new and potentially significant therapeutic target for this disease process.

Mycobacterium scrofulaceum infection presenting as lung nodules in a heart transplant recipient.

Pulmonary nodules have been reported in up to 10 percent of heart transplant recipients. Most are infectious, with opportunistic pathogens most common. Atypical mycobacteria have not been reported as the etiology of pulmonary nodules in a heart transplant recipient. We report a case of Mycobacterium scrofulaceum infection presenting as three discrete pulmonary nodules.

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.

Amiodarone-cyclosporine interaction in a heart transplant patient.

We report the case of a heart transplant patient whose cyclosporine clearance decreased by more than 50% after the institution of amiodarone therapy. This interaction necessitated a significant dosage reduction to maintain cyclosporine concentrations within the therapeutic range. To investigate the mechanism of the interaction, a cyclosporine-lipoprotein-binding determination was performed. The results suggest that drug displacement from competitive lipoprotein-binding sites is not responsible for the alterations in cyclosporine pharmacokinetics. Clearance data suggests, however, that the primary mechanism for the interaction is the inhibition cyclosporine metabolism by the cytochrome P-450 system. This report emphasizes the importance of reevaluating therapeutic drug regimens when new agents are added to prevent complications caused by drug interactions. If amiodarone and cyclosporine must be used concomitantly, cyclosporine levels must be monitored frequently, in anticipation of this interaction.

Characteristics of ventricular function in severe hemorrhagic shock.

Although left ventricular (LV) function appears altered by severe hemorrhagic shock (HS), the mechanisms of this dysfunction have been difficult to characterize. Depression in the LV function curve could be caused by altered diastolic or systolic function. It has been difficult to assess the systolic function, but the use of the rate and load independent index of contractility, Emax (the slope of the end-systolic pressure-dimension relationship), offers a new approach to the quantification of systolic mechanical performance. Emax and the LV diastolic pressure-strain relationship were measured in 15 chronically instrumented dogs by sonomicrometric and micromanometric techniques. Gradual LV unloading was obtained from transient vena caval occlusion. After control study, each dog underwent 2 hours of HS (mean aortic pressure 40 mm Hg), followed by reinfusion of all shed blood. Upon reinfusion, Emax was not decreased; however, all dogs had a significant decrease in LV compliance. During the next 4 days, the LV compliance of the eight survivors progressively returned toward control, while Emax remained stable. All seven nonsurvivors demonstrated progressive loss of LV compliance, and Emax was significant decreased prior to death. Cardiac contractility appeared improved immediately after shock, but a consistent decrease in compliance was observed. Reversal of abnormal diastolic function was demonstrated in all survivors and progressive depression in all nonsurvivors. Depression in systolic function was observed only in nonsurvivors immediately prior to death.

Tricuspid valve repair for biopsy-induced regurgitation after cardiac transplantation.

Tricuspid regurgitation is a recognized complication of cardiac transplantation. Damage to the tricuspid valve and subvalvar apparatus has been suggested as a possible cause. We have repaired the tricuspid valves of 2 patients in whom severely symptomatic tricuspid regurgitation developed after transplantation. Gore-Tex sutures were used to replace ruptured chordae anchoring the septal and posterior leaflets. The repair was supported with a Carpentier-Edwards ring. The repairs remain durable at 2 year and 3 years. Both patients demonstrated a similar lesion that we believe to be characteristic of endomyocardial biopsy-induced tricuspid regurgitation.

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.

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)

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.

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.

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.

Characterization of thromboxane A2/prostaglandin H2 receptors in human vascular smooth muscle cells.

The present study utilizes a newly synthesized TXA2/PGH2 mimetic, I-BOP, to characterize the TXA2/PGH2 receptor in suspensions of cultured human vascular smooth muscle cells. [125I]-BOP bound in a saturable and specific manner (Kd = 2.6 +/- 0.6 nM; Bmax = 33,540 +/- 6,200 sites/cell; 69 fmoles/mg protein, n = 12). Competition binding assays were performed with [125I]-BOP and the TXA2/PGH2 receptor antagonists SQ29548, L657925 and L657926 and the receptor agonist U46619. I-BOP induced concentration-dependent increases in intracellular free calcium which were inhibited by SQ29548. The results provide radioligand binding evidence for the presence of a TXA2/PGH2 receptor in human vascular smooth muscle cells.

Long-term results of aortic valve replacement.

Many studies document improved short- and long-term survival in patients with severe aortic stenosis or regurgitation after AVR. Despite this, AVR should be considered palliative because the valve prosthesis introduces the patient to a new disease process in which complications include thromboembolism, anticoagulant-related bleeding, infection, and structural deterioration. Significant refinements in valve prostheses have reduced but not eliminated these problems. Furthermore, improvements in surgical technique and myocardial preservation continue to decrease the risks of operation. Long-term improvement in ventricular function has been well documented after AVR and is probably responsible for the improvements in survival we now enjoy.

Diagnostic accuracy of phleborheography in deep venous thrombosis.

The clinical diagnosis of acute deep thrombophlebitis of the lower extremities is notoriously grossly inaccurate, even in experienced hands. Phleborheography (PRG) is one of the noninvasive diagnostic methods developed to make diagnosis accurate, noninvasive, and easily reproducible. The records of the first 272 patients studied by this method at South Fulton Hospital were examined, beginning June 1977 and ending August 1979. In those patients who had PRG and radiologic phlebography, the two methods were compared. Phlebography was considered as the standard for comparison. There were 36 patients who had both studies performed. Of the 36 patients studied, the PRG and the x-ray studies agreed in 34. Both were normal in 21 patients; and in 13 patients both were abnormal and in agreement. The studies did not agree in two of the 36 patients. There were none where the PRG was normal and the x-ray abnormal, and two where the PRG was abnormal and the x-ray normal. The diagnostic accuracy of a normal PRG in this study was 100 per cent, with no false-negatives. There were two false-positives with an accuracy of 87 per cent. The overall accuracy was 94 per cent. There were no complications.

CD3 monitoring and thymoglobulin therapy in cardiac transplantation: clinical outcomes and pharmacoeconomic implications.

INTRODUCTION: CD3 monitoring of antithymocyte globulin therapy in renal transplantation has been shown to be more cost-effective than standard regimens. The objective of this study was to evaluate CD3 monitoring with Thymoglobulin in cardiac transplantation. METHODS: Cardiac transplant patients who required antithymocyte globulin therapy were dose-adjusted to maintain absolute CD3 counts <25 cells/microL. Endomyocardial biopsies and hemodynamic parameters were used to assess efficacy. The incidences of hematological side effects, opportunistic infections, and malignancies were recorded; in addition we performed a cost comparison. RESULTS: Eight patients were treated with Thymoglobulin using CD3 monitoring to adjust the dosing. All patients responded with few side effects. Compared to standard dosing, CD3 monitoring allowed a 60% reduction in the average total dose and a 58% reduction in cost per patient. CONCLUSION: CD3 monitoring of Thymoglobulin therapy in cardiac transplant patients results in lower doses and reduced costs with equivalent efficacy and a low incidence of complications.

Postinfarction cardiac rupture after coronary revascularization.

Rupture of the myocardium is a catastrophic complication of acute myocardial infarction. Coronary revascularization has been increasingly utilized for the treatment of postinfarction angina. Further, myocardial infarction is a well known complication of coronary revascularization. Nonetheless, cardiac rupture after coronary revascularization has been rarely described. Described herein are three such cases with a review of the literature.

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.