Ischaemia or reperfusion: which is a main trigger for changes in nitric oxide mRNA synthases expression?

OBJECTIVE: To investigate alterations in endothelial nitric oxide synthase and inducible nitric oxide synthase mRNA expressions and nitric oxide release in the myocardium during ischaemia/reperfusion and determine whether these changes are ischaemic and/or reperfusion dependent. MATERIALS AND METHODS: Isolated rat hearts were perfused by a modified Langendorff system. Following 1 h of global cardioplegic ischaemia, left ventricle haemodynamic parameters were recorded at baseline and during 30 min of reperfusion. Levels of endothelial, inducible nitric oxide synthases mRNA expression and nitric oxide release were measured at baseline, after ischaemia and at 30 min of reperfusion. RESULTS: Global cardioplegic ischaemia caused a significant depression of left ventricular function and a decrease of coronary flow. Postischaemic intensities of the endothelial nitric oxide synthase mRNA bands were significantly lower than at baseline (P < 0.01). There were no significant differences in endothelial nitric oxide synthase mRNA band intensities immediately after ischaemia compared to the end of reperfusion, nor between the intensities of inducible nitric oxide synthase mRNA bands at baseline, at end of ischaemia and at end of reperfusion. Nitric oxide in the myocardial effluent was below detectable levels at all measured points. CONCLUSION: Ischaemic injury causes down-regulation of endothelial nitric oxide synthase mRNA expression, which is then associated with reduction of coronary flow during reperfusion, representing one possible mechanism of ischaemia/reperfusion injury. We did not find expected elevations of inducible nitric oxide synthase mRNA expression during ischaemia or reperfusion and we suggest that ischaemia/reperfusion injury is not associated with nitric oxide overproduction.

Comparison of vasoactive response of left and right internal thoracic arteries to isosorbide-dinitrate and nitroglycerin: an in vitro study.

OBJECTIVE: The internal thoracic artery (ITA) is the most important graft in coronary artery bypass grafting. Its distal region is, however, prone to vasospasm. We studied the effects of nitroglycerin (NTG) and isosorbide-dinitrate (DSDN) on distal segments of left versus right ITA. METHODS: Rings of distal segments (6 to 9 mm proximal to bifurcation) of the human left and right ITA were studied. After baseline contraction of the rings, achieved using 60 mmol/L of KCl, they were exposed to increasing doses of ISDN and NTG (10 to 100 microg/ml), and dose-response curves were recorded. RESULTS: The contractile response of left ITA rings to KCl were significantly lower than those of right ITA rings (1.87 +/- 0.25 g versus 3.5 +/- 0.61 g, p < 0.005). Both nitrates inhibited the contractile response in a concentration-dependent manner, with relaxing effects of ISDN higher than those of NTG (p < 0.01) in both left and right ITA rings. CONCLUSIONS: The distal segment of the left ITA is less prone to vasospasm than that of the right. ISDN has a considerably higher relaxant effect on this segment than NTG. We therefore recommend favoring high doses of ISDN over NTG as an antispastic measure.

Technical aspects of harvesting the radial artery with the harmonic scalpel.

BACKGROUND: Harvesting the radial artery (RA) with ultrasonic dissection with the Harmonic Scalpel reduces spasm induced by surgical handling. Topical exposure to phentolamine methanesulphonate (Regitine) exerts an additional effect of vasodilatation. METHODS: Between January and December 2002, the RA was harvested as a pediculated vessel with the Harmonic Scalpel in 145 consecutive patients undergoing myocardial revascularization. A fasciotomy of the pedicle was performed after harvest ing. A composite graft with the reverse free RA on the in situ left internal thoracic artery (ITA) was prepared before the construction of distal coronary anastomoses. The RA was then placed in a syringe filled with Regitine (0.07 microg/mL) for 10 minutes. \par RESULTS: The mean number of grafts/patient was 3.0. The mean number of RA anastomoses was 2.0/patient. Left ITA free flow was 105 +/- 34 mL/min. Regitine increased the RA free flow from 60 +/- 35 mL/min to 82 +/- 30 mL/min (P <.05). Fourteen patients underwent postoperative coronary angiography. All RA anastomoses were patent. CONCLUSION: The compound effect of RA harvesting with the Harmonic Scalpel and topical treatment with the alpha- blocking agent Regitine increases the RA free flow and significantly decreases intraoperative spasticity.

Midterm results of routine bilateral internal thoracic artery grafting.

BACKGROUND: Skeletonized dissection of the internal thoracic artery (ITA) decreases the occurrence of sternal devascularization, thus decreasing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. METHODS: From April 1996 to July 1999, 1000 consecutive patients underwent bilateral skeletonized ITA grafting. Of the 770 male and 230 female patients, 420 were older than 70 years, and 312 had diabetes. RESULTS: Operative mortality was 3.3%. Follow-up (40-78 months) revealed 79 late deaths, and the Kaplan-Meier 6-year survival rate was 88%. Cox regression analysis revealed increased overall mortality (early and late) in patients with preoperative congestive heart failure (risk ratio [RR], 2.13; 95% confidence interval [CI], 1.31-3.45), in patients with peripheral vascular disease (RR, 5.52; 95% CI, 3.31-9.19), and in patients older than 70 years (RR, 2.18; 95% CI, 1.37-3.47). Early postoperative morbidity included sternal infection (2.2%), cerebrovascular accident (1.6%), and perioperative myocardial infarction (1%). Multiple regression analysis showed repeat operation (odds ratio [OR], 7.5; 95% CI, 1.77-31.6) and chronic obstructive pulmonary disease (OR, 3.6; 95% CI, 1.27-10.75) to be independent predictors of sternal infection. During follow-up, angina returned in 95 patients, 24 of whom required reintervention (20 cases of percutaneous balloon angioplasty and 4 reoperations). Postoperative coronary angiography performed in 87 patients revealed an ITA patency rate of 91%. CONCLUSIONS: Bilateral skeletonized ITA grafting is associated with satisfactory early and midterm results. We do not recommend the use of this surgical technique in patients with chronic obstructive pulmonary disease.

Pretreatment with alpha-adrenergic blockers for prevention of radial artery spasm.

BACKGROUND: Radial artery (RA) conduits are prone to early vasospasm. Current intraoperative treatment with papaverine fails to inhibit postoperative RA constriction. Pretreatment with topical a-antagonist solutions can inhibit RA vasoconstriction and cause dilatation for a longer period than achieved with papaverine. METHODS: In 10 patients undergoing myocardial revascularization, the radial artery was harvested as a skeletonized vessel. A composite graft with reverse free RA on an in situ left internal thoracic artery was prepared before construction of distal coronary anastomoses. The RA pedicle was then put in a small syringe filled with Regitine (phentolamine methansulphonic, 0.07 mg/mL) ("Jacuzzi") and warmed by immersing the container in a warm saline bath for 8 to 15 minutes. The RA free flow was measured before and after topical treatment with Regitine. RESULTS: The mean number of grafts per patient was 2.9 (range 2 to 4). The mean number of radial anastomoses was 1.8 per patient. Left internal thoracic artery free flow was 110 +/- 29 mL/min. Regitine increased radial free flow from 49 +/- 35 to 77 +/- 30 mL/min (p < 0.01). Five patients underwent postoperative coronary angiography. All radial anastomoses were patent. CONCLUSIONS: Topical treatment of RA with Regitine increases RA free flow and is an effective intraoperative means of decreasing RA spasticity.

Arterial myocardial revascularization with in situ crossover right internal thoracic artery to left anterior descending artery.

BACKGROUND: The extra length obtained by skeletonizing the internal thoracic arteries (ITAs) enables versatile use of in situ bilateral ITAs for coronary artery bypass grafting, as the longer skeletonized right ITA more easily reaches the anastomotic site on the left anterior descending coronary artery. METHODS: Between April 1996 and November 1999, 365 consecutive patients underwent revascularization with bilateral in situ ITAs (29% of 1,250 grafting procedures performed with both ITAs in our department during this period). The right ITA was routed anterior to the aorta to graft the left anterior descending coronary artery, and the in situ left ITA was used to graft circumflex branches. Right coronary artery branches were grafted with right gastroepiploic artery or saphenous vein graft. The right ITA crossed the midline above the aorta at the most cranial point to avoid damage in case of a repeat sternotomy in the future. RESULTS: The operative mortality rate was 2.2% (8 patients). Postoperative morbidity included seven strokes (1.9%), eight sternal wound infections (2.2%), and four perioperative myocardial infarctions (1.1%). Follow-up (6 to 49 months) of 97% of hospital survivors showed a return of angina in 3%. Postoperative coronary angiography (22 patients) revealed a 95% patency rate of both ITAs. One-year and 4-year survival rates (Kaplan-Meier) were 95% and 92.4%, respectively. Important predictors of an early unfavorable event were chronic obstructive pulmonary disease, old age (> or = 70 years), emergency operation, and diabetes. Chronic obstructive pulmonary disease was the only independent predictor of sternal wound infection (odds ratio, 15; 95% confidence interval, 2.8 to 80). It also predicted decreased late survival (hazard ratio, 8.3; 95% confidence interval, 3 to 21.5). CONCLUSIONS: With skeletonized dissection of ITAs, the right ITA easily reaches the left anterior descending coronary artery for left-sided arterial revascularization with in situ bilateral ITAs. This procedure is safe, but we recommend avoiding its use in patients with chronic obstructive pulmonary disease.

Bilateral skeletonized internal thoracic artery grafting in 303 patients seventy years and older.

OBJECTIVES: Higher patency rates of the internal thoracic artery have led myocardial revascularization with bilateral internal thoracic arteries to be a procedure designated primarily for young patients. Fewer leg wound complications and sternal collateral flow preservation with the skeletonizing dissection technique can make bilateral internal thoracic artery grafting attractive also for elderly patients. METHODS: Between May 1996 and May 1998, 303 consecutive patients aged 70 years or older (mean age 75.5 years; range 70-92 years) underwent coronary artery bypass grafting with double skeletonized internal thoracic arteries. Forty-four (14.5%) patients were 80 years or older, and 89 (28%) had diabetes. The mean number of grafts was 3.1 per patient (2-6). RESULTS: Operative mortality was 2.6% (n = 8): it was higher for octogenarians (6.8%) than for younger patients (1.9%) (P =.06). The only significant preoperative predictors of early mortality were complicated percutaneous transluminal coronary angioplasty (P =.03) and preoperative use of intra-aortic balloon pumping (P =.03). Six patients (2%) had sternal wound infections for which chronic lung disease (P =.02) and emergency operation (P =.006) were the only significant predictors. Twenty-two (7.2%) late deaths occurred, and 1- and 3-year survivals were 93% and 90%, respectively. The 3-year survival of patients 80 years old or older was 92%. CONCLUSIONS: Bilateral grafting of the skeletonized internal thoracic artery carries relatively low morbidity and mortality in elderly patients and can be recommended for selected patients including octogenarians.

Combined repair of pectus excavatum and coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) in patients with severe pectus excavatum is a surgical challenge. A two-stage correction of sternal deformities and cardiac lesions has been described and myocardial revascularization through a left lateral thoracotomy is a valid alternative in urgent situations. We report a one-stage repair of severe pectus excavatum and CABG with the use of bilateral internal thoracic arteries in a young patient requiring urgent myocardial revascularization. The technical aspects and operative consideration are discussed.

Low-molecular-weight heparin for prosthetic heart valves: treatment failure.

There is no adequate substitute therapy for patients with prosthetic heart valves, in whom anticoagulation with warfarin or unfractionated heparin must be withheld. In the literature there are several reports describing successful treatment with low-molecular-weight heparin in patients with prosthetic heart valves. We report two cases of low-molecular-weight heparin treatment failure resulting in thrombosed prosthetic heart valves with stormy clinical presentations, who underwent successful valve replacements.

Routine use of bilateral skeletonized internal mammary arteries for myocardial revascularization.

BACKGROUND: Complete arterial myocardial revascularization without the use of saphenous veins grafts was primarily performed on selected patient populations such as the young and nondiabetic. In a recently developed surgical technique, the internal mammary artery is dissected gently as a longer skeletonized artery, providing greater versatility for complete arterial revascularization, without saphenous veins grafts. METHODS: We prospectively evaluated the impact of the routine use of double skeletonized internal mammary artery in 472 patients who underwent coronary artery bypass grafting between April 1996 and June 1997. Their average age was 65 years (30 to 87 years), 383 (83%) were men, and 89 (17%) women. One hundred sixty-nine (36%) of the patients were older than 70 years, and 145 (31%) were diabetic. The average number of grafts was 3.2 per patient (two to six grafts). RESULTS: Operative mortality was 1.7% (n = 8). The mortality of urgent and elective patients was 0.7% (3 of 410 patients), and that of emergency operations was 8.1% (5 of 62 patients; p < 0.01). There were three (0.6%) perioperative infarcts, and 6 patients (1.3%) sustained strokes. Sternal wound infection occurred in 8 patients (1.7%). Postoperative follow-up (1 to 25 months) was available in 462 patients (99%). Two-year actuarial survival was 96.8%, and 92% of the surviving patients are well and free of angina. Neither diabetes mellitus nor old age (>70 years) were significant independent predictors of any early or late untoward events. None of the 70 diabetic patients more than 65 years of age developed sternal wound infection. Chronic lung disease was found to be the only independent predictor for sternal infections. CONCLUSIONS: Routine use of bilateral skeletonized internal mammary artery is a safe replacement for the current myocardial revascularization technique even in the old and diabetic patients.

[Routine use of of two internal mammary arteries for coronary bypass grafting--one year experience at the Tel Aviv Medical Center].

The skeletonized internal mammary artery (IMA) is longer, and its immediate spontaneous blood flow is greater than that of the pedicled IMA, thus providing increased versatility for complete, arterial myocardial revascularization without the use of saphenous vein grafts. From April 1996 to May 1997, 583 patients underwent coronary artery bypass grafting here and in 415 (71%) complete arterial revascularization was achieved using bilateral skeletonized IMA. The right gastroepiploic artery was used in 57 (13%); there were 329 males (79%) and 86 women (21%); average age was 64 (30-87) and 175 (36%) were older than 70; 131 (32%) were diabetics. Average number of grafts was 3.2 (range 2-6 grafts). At 30 days, 5 (1.2%) had died and there had been 6 perioperative infarcts (1.4%), 5 CVA's (1.2%), and 6 had sternal wound infections (1.4%). Up to 1-12 months of follow-up was achieved in 409 (99%). Late mortality was 1.4% (of which 3 were noncardiac). 394 (97%) were angina-free at latest follow-up. We conclude that arterial revascularization using bilateral skeletonized IMA is safe, as postoperative morbidity and mortality are low, even in old and diabetic patients.