Nitric oxide: implications for vascular and endovascular surgery.

Nitric oxide has a key role in vascular homeostasis. It plays a protective role by suppressing abnormal proliferation of vascular smooth muscle following various pathological situations including atherosclerosis and restenosis after vascular interventions such as balloon angioplasty, stent deployment and bypass grafting. It also has strong antiplatelet and anti-thrombogenic properties. In this review, possible applications to daily vascular and endovascular surgery practice, including systemic use of NO donors, enhancing endogenous production of NO by L-arginine and gene therapy, local delivery strategies and coating stents and grafts with NO-delivering/enhancing chemicals are reviewed.

Approach to sinus of Valsalva aneurysms: a review of 53 cases.

OBJECTIVE: The reported experience with sinus of Valsalva aneurysms (SVAs) is limited. Our approach to this subset of patients and an algorithm-dependent classification are presented. METHODS: Between 1985 and 2000, 53 patients (mean age: 24+/-12; range 4--60) underwent repair for ruptured (64%) or non-ruptured (36%) SVA. Associated lesions were present in 21 patients; VSD in 18, moderate to severe aortic insufficiency in five, aortic stenosis in four (two subaortic membrane and one bicuspid valve), PDA in two, mitral insufficiency in one, tetralogy of Fallot in one and endocarditis in one. Operative procedures included simple or Teflon pledgetted direct suturing (31 cases; 58%), patch repair (21 cases; 40%), and stentless porcine bioprosthetic aortic root replacement in a case with extensive involvement and aortic root distortion (2%). Concomitant procedures were VSD repair in 18 patients, aortic valve replacement in four, aortic valve resuspension in three, subaortic membrane resection in two, PDA ligation in two, mitral annuloplasty in one and total correction in one. RESULTS: Early mortality was 1.9%. A permanent pacemaker was inserted in one patient due to complete heart block. The survivors were followed up for 8.2+/-5 years (range: 21 days to 15 years). There were three reoperations due to suture dehiscence; patch repair was undertaken in these patients with no further unfavorable consequences. All patients were in NYHA Class I or II as of their last follow-up. CONCLUSIONS: Repair of SVA can be performed with an acceptably low operative risk and a good symptom-free long-term outcome expectation. Echocardiography provides all the necessary details for diagnosis. Dual exposure/patch repair strategy is advocated in the ruptured cases.

Closed commissurotomy versus balloon valvuloplasty for rheumatic mitral stenosis.

BACKGROUND AND AIM OF THE STUDY: Closed mitral commissurotomy (CMC) and percutaneous mitral balloon valvuloplasty (PMBV) were compared by their initial results and Doppler echocardiographic data obtained at one week and one year after the procedure. METHODS: Of 580 patients with severe rheumatic mitral stenosis, 280 underwent CMC and 300 PMBV. The mean pre-procedural transmitral gradient (TMG) was 21 +/- 6 mmHg in the CMC group and 20 +/- 5 mmHg in the PMBV group (p = 0.6); the mean mitral valve area (MVA) was 1.1 +/- 0.2 cm2 in both groups. RESULTS: Mortality was 0.7% after CMC and 0.3% after PMBV; the primary success rates were 98.3% and 89% respectively (p <0.0001). Two CMC patients and three PMBV patients underwent emergency mitral valve replacement. At the first week, the mean TMG was decreased to 4 +/- 3 mmHg in the CMC group, and to 5.8 +/- 2 mmHg in the PMBV group (p <0.0001). The mean MVA was increased to 2.5 +/- 0.5 cm2 after CMC, and to 2.1 +/- 0.4 cm2 after PMBV (p <0.0001). After one year, TMG was 5.4 +/- 4 mmHg in the CMC group (p <0.0001) and 7.1 +/- 3 mmHg in the PMBV group (p <0.0001); MVA was 2.3 +/- 0.5 cm2 (p <0.0001) and 1.9 +/- 0.4 cm2 (p <0.0001), respectively. The results of CMC were significantly better (p <0.0001) with regard to TMG and MVA at these times. A significant decrease was also seen in mean left atrial diameter and pulmonary artery pressure in both groups (p <0.0001). CONCLUSION: Although satisfactory results can be achieved using either approach, CMC provides a higher primary success rate, greater MVA augmentation, and better technical control during the procedure, while reducing the cost. PMBV shortens in-hospital stay and eliminates the risk imposed by thoracotomy and anesthesia. Therefore, in our practice, when surgical intervention is contraindicated due to associated problems, PMBV may be the preferred approach, but exposure to radiation may be of concern in pregnant patients.

Long-term patency of sequential and individual saphenous vein coronary bypass grafts.

OBJECTIVES: The long-term patency rates for individual and sequential saphenous vein grafts (SVG) as coronary bypass conduits are angiographically compared; the impact of native coronary vessel characteristics is investigated. METHODS: A total of 875 distal coronary anastomoses on 500 SVGs were assessed in 430 patients at an average of 5.8+/-3 years after a coronary revascularization procedure. RESULTS: The patency rates of sequential conduits were markedly higher than those of individual ones (82 vs. 68%, P=0.0005). Also, the anastomoses on the sequential conduits had better patency (75 vs. 68%, P=0.03). This difference was even more pronounced in coronary arteries of poor quality and small (<1.5 mm) diameter (57 vs. 28% for the sequential grafts and individual grafts, respectively, P=0.001). Also, when the most distally located coronary artery on a sequential graft was of poor run-off, the patency rate for the entire conduit was considerably low (42.5%). CONCLUSIONS: The patency of a sequential vein graft conduit is generally better than that of an individual one, especially for poor run-off coronary vessels, provided that the most distally located anastomosis is done on a good coronary artery in terms of quality and diameter. Using a minimal length of conduits is another advantage. However, failure of a single sequential conduit jeopardizes all the anastomoses along that graft segment. Besides, sequential grafting is technically more demanding, and the technical expertise in performing a sequential anastomosis is probably among the important determinants of short- and long-term patency.

Mid-term results of partial left ventriculectomy in end-stage heart disease.

OBJECTIVE: Immediate and mid-term effectiveness of partial left ventriculectomy (PLV) is assessed in 27 idiopathic dilated cardiomyopathy patients. METHODS: All patients were in New York Heart Association (NYHA) class III (17) or IV (ten). The average left ventricular ejection fraction (LVEF) was 19+/-4% by MUGA, and 23+/-4% by digital echocardiography. The mean end-systolic volume (LVESV) was 259+/-66 ml and the mean end-diastolic volume (LVEDV) was 342+/-83 ml. Mitral valve replacement was a routine part of the procedure. RESULTS: Operative mortality was 18.5%, a LVEDP>25 mmHg, left atrial diameter>55 mm, pulmonary artery systolic pressure>40 mmHg, congestive hepatomegaly and NYHA class IV being the mortality predictors. Three-year Kaplan-Meier survival was 64+/-10%, including operative mortality; freedom from congestive heart failure was 65+/-11%. Functional status improved from 3.2+/-0.4 to 1.5+/-0.6 (P=0.0003). The mean LVEF was dramatically increased after PLV (to 40+/-4%, P=0.0001); LVESV was decreased to 90+/-30 ml (P<0.0001) and LVEDV to 160+/-49ml (P<0.0001). This improvement was sustained during the first 30 months. CONCLUSIONS: PLV is a reasonable approach for end-stage patients, providing sustained dramatic changes in ventricular geometry and functional capacity, especially in the absence of compromised right and diastolic left heart functions. Routine replacement of the mitral valve allows a more liberal ventriculectomy and eliminates mitral regurgitation, and this may help minimize ventricular distention.

Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemia-reperfusion.

OBJECTIVE: Alterations in nitric oxide synthesis, endothelial adhesivity and pulmonary hemodynamics are investigated in an animal model of lung ischemia-reperfusion. METHODS: Two sets of rats, each containing seven animals, were either subjected to unilateral pulmonary ischemia and reperfusion (Study Group) or underwent the same surgical procedure without ischemia (Control Group). Pulmonary artery pressure (PAP), pulmonary blood flow (PBF) trend, NOS-2, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) and cGMP expression of the reperfused lung tissue and, final paO(2) were compared between the two groups. RESULTS: ICAM-1 expression was increased (369+/-114 vs. 115+/-65; P=0.02), NOS-2 expression and tissue cGMP levels were decreased (377+/-44 vs. 452+/-54; P=0.03 and 7.8+/-3.5 vs. 9.4+/-2.3 pmol/ml; P=0.03, respectively) and MPO activity was increased (2.7+/-0.9-3.5+/-0.8; P=0.03) in the reperfused lungs. Pulmonary artery pressure was 15+/-7 mmHg in the Control Group vs. 22+/-16 mmHg in the Study Group (P=0.04) at the 30th min of reperfusion. Pulmonary blood flow was greater in the Study Group at the beginning of reperfusion (9.5+/-4.1 vs. 7.1+/-3.1 ml/min at the 30th min) but considerably reduced thereafter (3.2+/-1. 4 vs. 6.2+/-2.1 at the 60th minute and 2.9+/-1.6 vs. 5.8+/-1.9 at the 120th min). At the end of the experiment, paO(2) was 95+/-30 in the Control Group vs. 71+/-32 in the Study Group (P=0.03). CONCLUSIONS: These data establish that nitric oxide synthesis was suppressed after reperfusion. Pulmonary blood flow was first increased and then reduced. A parallel increase in MPO and ICAM-1 indicated proinflammatory reaction. Decreased tissue cGMP level was consistent with the suppressed NOS-2 production. Organ function was negatively influenced as represented by the decreased oxygenation, probably due to no-reflow phenomenon.

Effects of mast cell membrane stabilizing agents in a rat lung ischemia-reperfusion model.

BACKGROUND: The aim of this study was to test the hypothesis that agents which stabilize the mast cell membrane may modulate the phenotype of the vascular wall in a lung ischemia-reperfusion model, including altering expression of endothelial and leukocyte adhesion receptors and the inducible nitric oxide synthase (NOS-2). METHODS: Three sets of rats were given either intravenous saline (group A), ketotifen (group B), or cromolyn (group C), respectively. The left pulmonary artery was ligated temporarily and reopened after 2 hours of ischemia. Then, after a 2-hour period of reperfusion, the left lung was excised. ICAM-1 and NOS-2 were measured at the protein level by Western blotting, and cGMP levels were measured by enzyme-linked immunosorbent assay in the lung tissue specimens for each drug group. RESULTS: ICAM-1 expressions, determined as the intensity of a given band on the Western blot, were 197+/-59 in group B and 195+/-83 in group C versus 369+/-114 in group A (p = 0.002 for analysis of variance). In contrast with ICAM-1, NOS-2 expression was increased by ketotifen or cromolyn treatment (464+/-82 in group B and 507+/-93 in group C, compared with 377+/-44 for group A, p = 0.007). The finding of increased NOS-2 expression in groups B and C is consistent with the observed increase in tissue cGMP levels in the same groups (1.92+/-0.9 pmol/mL for group A versus 7.8+/-3.5 pmol/mL for group B, and 12.4+/-5.8 pmol/mL for group C, p = 0.0004). CONCLUSIONS: These data establish that mast cell stabilizing agents modulate the vascular phenotype in the setting of pulmonary ischemia and reperfusion by decreasing ICAM-1 expression, augmenting expression of NOS-2, and increasing tissue cGMP levels. As decreasing ICAM-1 expression and increasing cGMP levels have proven useful to limit proinflammatory mechanisms of tissue injury, mast cell stabilizing agents may provide a new therapeutic option to improve organ function in the setting of reperfusion.

Membrane stabilization in harvested vein graft storage: effects on adhesion molecule expression and nitric oxide synthesis.

OBJECTIVE: Expression of cellular adhesion molecules in human saphenous vein grafts may occur even during harvesting and storage, before the grafts have been implanted as bypass conduits. This may play a role in graft adaptation to arterial flow conditions, which may play an important role in late graft patency. In this study, ketotifen, a mast cell membrane stabilizing agent was studied for its effects on reducing endothelial reactivity during storage of harvested vein graft segments. METHODS: Human saphenous vein grafts, obtained from seven patients and then divided into two equal parts of control and study specimens, were stored in either heparinized blood (Group A) or heparinized blood containing 100 microg/ml ketotifen (Group B) for 1 h at room temperature. Specimens were analyzed by Western blotting to quantify ICAM-1, E-selectin, P-selectin, VCAM-1, and inducible nitric oxide synthase (NOS-2) expression, as well as tissue cGMP levels in response to topical application of an endothelium-independent vasodilator. RESULTS: ICAM-1, E-selectin and P-selectin expression did not differ between the groups. However, VCAM-1 expression was significantly lower in Group B (460 +/- 29 vs. 289 +/- 50, P = 0.01). NOS-2 expression (488 +/- 64 vs. 577 +/- 38, P = 0.02) and tissue cGMP levels (2.2 +/- 0.6 pmol/ml vs. 5.7 +/- 1.7 pmol/ml, P = 0.01) in response to nitroglycerin (24 +/- 10% vs. 11 +/- 5%, P = 0.02) were higher in Group B. CONCLUSIONS: Of all of the adhesion receptors studied, only VCAM-1 expression was reduced by a mast cell membrane-stabilizing agent, perhaps because of activation of the venous endothelium during harvest prior to ketotifen exposure. However, ketotifen also augmented NOS-2 expression, increased tissue cGMP levels in response to nitroglycerin. These actions may improve vascular homeostasis in the venous graft, suggesting the possibility that this strategy may improve long-term graft patency.

Coronary artery bypass grafting on the beating heart without the use of extracorporeal circulation: review of 2052 cases.

OBJECTIVE: A total of 2052 patients operated on with the off-pump technique (coronary artery bypass grafting on the beating heart without the use of extracorporeal circulation) between June 1993 and March 1996 are retrospectively reviewed. Predictors for early mortality, perioperative myocardial infarction, and low cardiac output state were statistically analyzed. METHOD: Our indications for an off-pump procedure were either patients with technically suitable coronary lesions (the vast majority) or patients who could not tolerate cannulation, hypothermia, or cardiopulmonary bypass because of the poor left ventricular function (198 patients) and/or associated diseases or conditions (73 patients). RESULTS: Overall operative mortality was 1.9% and perioperative myocardial infarction occurred in 59 patients (2.9%). According to logistic regression analysis, associated bronchial asthma (p = 0.0001), hypertension (p = 0.05), poor quality of the left anterior descending artery (p = 0.02), and ungrafted circumflex coronary artery disease (p = 0.007) were the early mortality predictors. Nonbypassed circumflex disease was also associated with a high incidence of perioperative myocardial infarction and low cardiac output state. No homologous blood or packed red cell transfusion was required in 74.2% of the patients. CONCLUSION: On the basis of the presented data, off-pump coronary artery bypass grafting appeared to be a safe and effective technique in selected patients with appropriate coronary lesions.

Optimization of synchronization delay in latissimus dorsi dynamic cardiomyoplasty.

BACKGROUND: Optimal synchronization delay (SD) for triggering the implanted cardiomyostimulators in patients undergoing latissimus dorsi dynamic cardiomyoplasty has not been clearly defined. Generally a synchronization delay time of 45 to 60 ms is used in the current practice, in which the implanted cardiomyostimulator stimulates the latissimus dorsi muscle 45 to 60 ms after mitral valve closure acquired with M-mode echocardiography. We investigated the effect of shortening or prolonging the delay time on cardiac functions. METHODS: We studied 10 patients who were in their first 2 years postoperatively. Three values for SD (SD = 0 ms, 45 to 60 ms, and 150 to 160 ms) were echocardiographically evaluated for their influence on both systolic and diastolic left ventricular parameters. RESULTS: Ejection fractions were 0.27 +/- 0.07, 0.28 +/- 0.07, and 0.32 +/- 0.06; peak aortic velocities were 0.85 +/- 0.8, 0.86 +/- 0.11, and 0.92 +/- 0.8 m/s; and velocity-time integrals were 0.16 +/- 0.03, 0.16 +/- 0.03, and 0.19 +/- 0.03 m for the SD values of 0, 45 to 60 ms, and 150 to 160 ms, respectively. Diastolic parameters were also measured. Isovolumetric diastolic relaxation time was 97.5 +/- 49, 97.20 +/- 44, and 111.8 +/- 49 ms; deceleration time was 83.67 +/- 32, 88.48 +/- 35, and 92.68 +/- 34 ms; and ratio or velocity-time integral of e wave to velocity-time integral of a wave was 3.09 +/- 0.98, 2.48 +/- 0.69, and 2.38 +/- 0.65 for the SD values of 0, 45 to 60 ms, and 150 to 160 ms, respectively. Systolic functions were better when SD was set at 150 to 160 ms, but there was a diastolic compromise. On the other hand, diastolic parameters were more favorable when SD = 0 (i.e., cardiomyostimulator triggered without delay) but the systolic assist was suboptimal. Systolic and diastolic parameters seemed relatively well-balanced with the current practice of setting the synchronization delay at 45 to 60 ms. CONCLUSIONS: The most favorable systolic effects were obtained with a prolonged delay of synchronization (150 to 160 ms), at some expense of diastolic functions. On the other hand, with a short or absent delay, diastolic parameters were improved but systolic parameters became suboptimal. Therefore, the current practice of setting the SD between 45 and 60 ms after echocardiographic mitral valve closure is suggested for the optimal timing for cardiomyostimulator stimulation in patients who have undergone latissimus dorsi dynamic cardiomyoplasty. Yet a great deal of individualization is necessary, and fixed preset values cannot definitely be determined because one setting does not fit all patients.

Left ventricular aneurysm repair: an assessment of surgical treatment modalities.

OBJECTIVE: Different closure techniques (linear vs. circular), as well as the efficacy of revascularization in the left ventricular aneurysm repair, with regard to immediate and mid-term results, were assessed and factors having influence on the early mortality and morbidity and survival were analyzed. METHOD: Between January 1991 and November 1996, 248 patients underwent surgical repair for postischemic left ventricular aneurysm. A total of 26 of them were female (10.50%). Linear closure was employed in 121 patients (48.8 %) and circular (patch endoaneurysmorraphy) closure in 127 (51.2%). Coronary revascularization was added in 203 (81.9%) cases. Patients were followed for an average follow-up time of 39.3 months. RESULTS: Early mortality rate was 6% (15 patients). The difference in mortality rate by the repair method was not statistically significant (8.3% in the linear closure group and 3.9% in the circular closure group, P = 0.15). Absence of preoperative angina pectoris (P = 0.029), dyspnea as the presenting symptom, a preoperative left ventricular segmental wall motion scoring of 14 or greater, a cardiopulmonary bypass duration exceeding 2 h (P = 0.004), an aortic clamping time exceeding 1 h (P = 0.026) were associated with early mortality. Concomitant coronary revascularization had no effect on early mortality. However, low cardiac output state was less frequent in patients with concomitant coronary revascularization (P = 0.022). Functional status improved in both groups. Follow-up extending to 81st month revealed no difference in survival between the groups (84% for linear closure group and 92% in circular closure group, including operative mortality, P = 0.12). However, functional status improvement was better in the patients who underwent circular repair (P = 0.0077). Revascularization appeared as having no important influence on both survival and functional status. A preoperative left ventricular segmental wall motion scoring of 14 or greater was associated with a higher incidence of early mortality, low cardiac output syndrome and poor long-term survival. CONCLUSION: Left ventricular aneurysm repair is an important therapeutic intervention and can be performed with reliable results, regardless of repair method, either linear or circular. Long term results revealed better functional status in circular repair group. Concomitant coronary revascularization reduced the incidence of low cardiac output state. Performance of the unaffected regions of myocardium was found to be an important determinant of both early and late outcome.

A comparison of the early and midterm results after dynamic cardiomyoplasty in patients with ischemic or idiopathic cardiomyopathy.

OBJECTIVE: The main goal of this study is to determine the efficiency of the cardiomyoplasty procedure on patients with cardiomyopathy of different origins (ischemic and idiopathic origins). METHOD: Between June 1993 and August 1995, 24 patients underwent dynamic cardiomyoplasty with the left latissimus dorsi muscle in our institution. Early and midterm results, as well as the changes in hemodynamics and functional status during follow-up, were compared. RESULTS: Early mortality rate was 20.8% (five patients). Concomitant coronary revascularization, a preoperative left ventricular ejection fraction below 20%, and a functional capacity of class IV (intermittently) were associated with early mortality. The mean follow-up time was 17.3 months. Survival analysis (including early mortality) extending to the twenty-fourth month revealed no difference between the ischemic and idiopathic groups (55% vs 85%, respectively, p = 0.09). Functional status improved in the both groups. Ejection fractions were improved after cardiomyoplasty in all patients, regardless of their cause. Cardiac indices were higher 6 months after the operation. Changes in pulmonary capillary wedge pressure, peak pulmonary artery pressure, and left ventricular end-diastolic volume were not significant. CONCLUSION: Although cardiomyoplasty improves functional capacity and hemodynamics in patients with both idiopathic and ischemic cardiomyopathy, the idiopathic group is thought to achieve optimal benefit with regard to lower complication rates and lower early mortality expectancy owing to the absence of concomitant coronary revascularization.

Comparative study on cardiomyoplasty patients with the cardiomyostimulator on versus off.

BACKGROUND: A major concern in evaluating dynamic cardiomyoplasty has been whether the synchronous stimulation of latissimus dorsi muscle is essential for benefit or not. We studied 10 patients to determine the efficacy of the systolic augmentation generated by the synchronous electrical stimulation of the latissimus dorsi muscle. METHODS: Left ventricular ejection fraction, end-systolic and end-diastolic volume indexes, and stroke volume index obtained during resting, peak exercise, and recovery periods ("on" values) were compared with those obtained 1 week after cessation of electrical stimulus ("off" values). Double product and estimated total body oxygen consumption at peak exercise were also calculated and compared. RESULTS: Higher ejection fractions (0.36 +/- 0.07 versus 0.33 +/- 0.06 at rest, 0.40 +/- 0.07 versus 0.33 +/- 0.07 at peak exercise, and 0.37 +/- 0.06 versus 0.31 +/- 0.06 at recovery).(ABSTRACT TRUNCATED)

Comparison of the early results of coronary artery bypass grafting with and without extracorporeal circulation.

To compare the safety and efficacy of coronary artery bypass grafting without using extracorporeal circulation with standard cardiopulmonary bypass technique, based on certain early postoperative criteria, we designed a fully randomized and prospective study on two similar groups of 25 patients (off-pump and on-pump groups). The groups were compared for hemodynamic data (cardiac index, systemic vascular resistance, left- and right-ventricular stroke-work indices, inotropic and mechanical support needs) and enzyme levels (CK-MB and SGOT), as well as mortality, perioperative infarction rate, homologous transfusion requirements, and the symptomatology in the first follow-ups. There was no mortality or perioperative myocardial infarction in either group. Inotropic (25% vs. 4%) and mechanical (4% vs. 0) support requirements and homologous blood consumption (percentages of patients that needed no transfusion: 20% vs. 72%) were greater in the on-pump group. Results were otherwise similar. It is concluded that, in technically suitable cases, off-pump coronary artery bypass surgery is as safe and efficient as the standard on-pump technique and can be used in particular when cannulation, hypothermia, or cardiopulmonary bypass must be avoided. With these properties, this technique could take an important place in the cardiac surgeon's armamentarium.