New evidence for the role of TNF-alpha in liver ischaemic/reperfusion injury.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) plays a key role in causing ischaemia/reperfusion (I/R) injury. I/R also causes activation of xanthine oxidase and dehydrogenase (XDH + XO) system that, via generated free radicals, causes organ damage. We investigated the effect of ischaemia, reperfusion and non-ischaemic prolonged perfusion (NIP) on TNF-alpha and XDH + XO production in an isolated perfused rat liver model. MATERIALS AND METHODS: Rat livers underwent 150 min NIP (control group) or two hours of ischaemia followed by reperfusion (I/R group). TNF-alpha (TNF-alpha mRNA and protein level), XDH + XO production and bile secretion were determined in tissue and effluent at baseline, at 120 min of ischaemia, after 30 min of reperfusion (I/R group) and after 120 and 150 min of prolonged perfusion (control). RESULTS: Unexpectedly, neither ischaemia nor reperfusion had any effect on TNF-alpha production. TNF-alpha in effluent was 11 +/- 4.8 pg mL(-1) at baseline, 7 +/- 3.2 pg mL(-1) at the end of ischaemia, and 13 +/- 5.3 pg mL(-1) after 30 min of reperfusion. NIP, however, caused a significant increase of TNF-alpha synthesis and release. TNF-alpha effluent level after 120 and 150 min of perfusion was 392 +/- 78.7 pg mL(-1) and 408 +/- 64.3 pg mL(-1), respectively. TNF-alpha mRNA in tissue was also significantly elevated compared to baseline levels (1.31 +/- 0.2 P < 0.001 and 1.38 P < 0.002, respectively). Decrease of liver function (expressed by bile secretion) during I/R and NIP was accompanied by significant XDH + XO elevation. CONCLUSION: This is the first evidence that NIP, and not I/R, is the decisive trigger for TNF-alpha production. This study leads to a better understanding of pathogenesis of liver I/R and perfusion damage.

Routine use of bilateral skeletonized internal thoracic artery grafting: long-term results.

BACKGROUND: Skeletonized harvesting of the internal thoracic artery (ITA) decreases the severity of sternal devascularization, thus reducing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. METHODS AND RESULTS: Between 1996 and 2001, 1515 consecutive patients underwent skeletonized bilateral ITA grafting. Of the 1179 male and 336 female patients, 641 (42.3%) were >70 years of age, and 519 (34.2%) had diabetes mellitus. Operative mortality was 2.8%. Early postoperative morbidity included sternal infection (1.6%), cerebrovascular accident (3%), and perioperative myocardial infarction (1%). Multiple regression analysis showed chronic obstructive pulmonary disease (odds ratio, 11.3; 95% confidence interval [CI], 4.45 to 28.55), repeat operation (odds ratio, 12.7; 95% CI, 3.25 to 49.56), and diabetes mellitus (non-insulin dependent: odds ratio, 4.64; 95% CI, 1.85 to 11.59; insulin dependent: odds ratio, 6.9; 95% CI, 1.35 to 35.27) to be associated with increased risk of sternal infection. Follow-up (between 5 and 12 years) revealed 305 late deaths. Kaplan-Meier 10-year survival rates for patients <65, 65 to 74, and >75 years of age were 87%, 75%, and 52%, respectively. Cox regression analysis revealed increased overall mortality (early and late) in patients with peripheral vascular disease (hazard ratio [HR], 1.8; 95% CI, 1.39 to 2.33), patients >75 years of age (HR, 7.23; 95% CI, 4.16 to 12.55), those undergoing repeat operations (HR, 2.22; 95% CI, 1.27 to 3.89), patients with preoperative congestive heart failure (HR, 1.64; 95% CI, 1.29 to 3.75), and those with chronic renal failure (HR, 1.52; 95% CI, 1.11 to 2.01). Operations performed without cardiopulmonary bypass were associated with better postoperative survival (HR, 0.66; 95% CI, 0.49 to 0.87). CONCLUSIONS: Bilateral ITA grafting is associated with low morbidity and good long-term results. Use of skeletonized bilateral ITA is appropriate for the elderly and most patients with diabetes; however, it is not recommended for repeat operations or for patients with chronic obstructive pulmonary disease.

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.

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.

Protamine-induced cardiotoxicity is prevented by anti-TNF-alpha antibodies and heparin.

BACKGROUND: We investigated the role of tumor necrosis factor alpha (TNF-alpha) in protamine-induced cardiotoxicity and the possibility of preventing or decreasing this effect by anti TNF-alpha antibodies and heparin. METHODS: Isolated rat hearts were perfused for 60 min with Krebs-Henseleit solution (KH). The control group was perfused with KH alone, the KH > protamine > KH group was treated from the 20th to the 40th minute with protamine, and the KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF group was treated the same as the KH > protamine > KH group but with anti-TNF-alpha antibodies added throughout perfusion. The KH + heparin > protamine + heparin > KH + heparin group was treated the same as the KH > protamine > KH group but with heparin added to KH throughout perfusion. The KH > protamine > KH + heparin was perfused the same as the KH> protamine > KH group but with heparin added to KH for the last 20 min. Left ventricular (LV) function and coronary flow were measured every 10 min. TNF-alpha was measured in the coronary sinus effluent. Left ventricular TNF messenger RNA was determined in the control and KH > protamine > KH groups at baseline and after the 40-min perfusion. RESULTS: Protamine caused a significant decrease of peak systolic pressure and dP/dt (to 25% of baseline). Significant amounts of TNF-alpha in the effluent in the KH > protamine > KH group (102.3 +/- 15.5 pg/min) and TNF messenger RNA expression in left ventricular samples were detected. TNF-alpha was below detectable concentrations in the control, KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF, and KH + heparin > protamine + heparin > KH + heparin groups. TNF-alpha concentrations correlated with depression of LV peak systolic pressure (r = 0.984; P = 0.01) and first derivate of the increase of LV pressure (r = 0.976; P = 0.001). Heparin improved LV recovery and decreased protamine-induced TNF-alpha release (KH > protamine > KH + heparin group). CONCLUSIONS: Anti-TNF-alpha antibodies and heparin prevent protamine-induced TNF-alpha release and depression of LV function. Heparin improves protamine-induced depression of cardiac function.

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.

Composite arterial grafting with double skeletonized internal thoracic arteries.

OBJECTIVES: Composite arterial grafting is a surgical technique for arterial myocardial revascularization, in which free arterial conduits are proximally anastomosed end-to-side to an intact internal thoracic artery (ITA). This report describes technical aspects and results of composite grafting using bilateral skeletonized ITAs. METHODS: From April 1996 to February 1999, 1057 patients underwent coronary artery bypass grafting (CABG) using bilateral skeletonized internal thoracic arteries. In 600 of them (57%), composite arterial grafting was performed. There were 452 men and 148 women. The mean age was 69 +/- 7 years. Two-hundred and six patients (34%) were diabetics, 84 (14%) had severe left ventricular dysfunction (ejection fraction of < 35%), and 26 (4.3%) underwent emergency operations. In 574 patients, the right ITA was used as a free graft connected to the in-situ left ITA. In 26, the free left ITA was attached to the in-situ right ITA, and in 38, mini-composite grafts (free distal left ITA on the left ITA, or free distal right ITA on the right ITA) were constructed. The average number of grafts was 3.0/patient (range, 2--6). RESULTS: The operative mortality was 2.8% (n = 17), and there were ten (1.7%), deep sternal wound infections. The mean follow-up was 25 months (range, 14--36 months). The 3-year survival was 92.5%. Ninety-seven percent of the surviving patients were angina-free. CONCLUSIONS: We currently perform this surgery routinely in most patients referred for CABG, and regard bilateral skeletonized internal thoracic arteries as the most appropriate arterial conduits for the composite technique.

Protamine cardiotoxicity and nitric oxide.

OBJECTIVES: The purpose of this study is to assess the role of the nitric oxide (NO) pathway in protamine-induced cardiotoxicity and to formulate a possible explanation for this adverse effect. METHODS: Isolated rat hearts were perfused by Krebs--Henseleit (KH) solution using a modified Langendorff model. They were randomized into three groups: A, 40 min perfusion with KH solution; B, 20 min perfusion with KH solution and 20 min with protamine; C, as B but Ng-monomethyl-L-arginine (L-NMMA), a non-selective inhibitor of the NO pathway, was added during 40 min of the perfusion period. Left ventricular (LV) function was measured every 10 min. NO and tumor necrosis factor-alpha (TNF) were detected in the effluent from the coronary sinus (CS) and in the supernatant of the cardiac myocytes culture. Nitric oxide synthases (NOS) mRNA levels were determined in groups A and B from LV samples at baseline and after 40 min of perfusion. RESULTS: We found that protamine at a dose of 12 microg/ml causes significant depression of LV function (decreased peak systolic pressure to 22.5+/-3.2% and dP/dt max to 22.9+/-3.1%). L-NMMA did not prevent protamine cardiotoxicity. NOS mRNA was not detected from LV samples in any group. The NO in the effluent from the CS and from the supernatant of the cardiomyocytes culture was below detectable levels. However, a significant amount of TNF was measured in the effluent from the CS (108+/-17 pg/min for group B and 117+/-13 pg/min for group C) and in the supernatant of the cardiomyocytes culture (65+/-21 pg/ml). CONCLUSIONS: This study suggests that direct protamine-induced cardiotoxicity does not depend on the NO pathway. Our finding that protamine induced TNF release by cardiomyocytes can shed new light on the understanding of protamine cardiotoxicity.

Vasoactive response of different parts of human internal thoracic artery to isosorbide-dinitrate and nitroglycerin: an in-vitro study.

OBJECTIVE: The left internal thoracic artery (LITA) is the most important graft for coronary artery bypass grafting (CABG). Its distal region is, however, prone to vasospasm. The effect of nitroglycerin (NTG) and isosorbide-dinitrate (ISDN) on different segments of this region was studied. METHODS: Rings of three segments of the LITA were studied: 6-9 mm proximal to the bifurcation (part A); 1-3 mm proximal to the bifurcation (part B); and 3-6 mm distal to the bifurcation (part C). After baseline, maximal contraction of the rings was achieved using 60 mmol/l of KCl, they were exposed to increasing doses of ISDN and NTG (10-100 microg/ml), and dose-response curves were recorded. RESULTS: The contractile response of part A to KCl was significantly lower than that of parts B and C (1.87+/-0.25 versus 4.05+/-0.39 and 7.64+/-0.54 g, respectively; P<0.001). Both nitrates inhibited the contractile response in a concentration-dependent manner. The relaxing effects of both nitrates on part A was most pronounced (P<0.01), with the effect of ISDN being higher than that of NTG (P<0.01). CONCLUSIONS: The region 6-9 mm proximal to the LITA bifurcation is less prone to vasospasm, and has greater relaxation responses to ISDN and NTG than the more vasospastic distal parts of the LITA. We recommend avoiding the use of the very distal part of this artery during CABG, and to use high doses of ISDN rather than NTG as an anti-spastic measure.

Effect of age on outcome of bilateral skeletonized internal thoracic artery grafting.

BACKGROUND: Elderly patients are considered to be at higher risk for coronary artery bypass grafting. Surgical techniques of arterial myocardial revascularization without vein grafts were primarily reserved for the young. This report evaluates the impact of age on the outcome of 634 consecutive patients who underwent double skeletonized internal thoracic artery grafting between April 1996 and December 1997. METHODS: Patients were stratified into five age groups: One hundred ninety-six were less than 60 years of age, 98 between 60 and 65 years, 132 between 65 and 70 years, 116 between 70 and 75 years, and 92 were older than 75 years. The groups did not differ with regard to preoperative risk factors. RESULTS: Hospital mortality was 2.5% (n = 16). Mortality of urgent and elective operations was 1.6%, and that of emergency operations was 9.7% (p < 0.001). There were 7 (1.1%) myocardial infarctions, 9 strokes (1.4%), and 10 deep sternal wound infections (1.6%). Using the Mantel-Haenszel test, there was no relation between age and hospital mortality, myocardial infarctions, strokes, or sternal infections. A correlation was found between advanced age and early unfavorable events (6.7%, 7.2%, 12.9%, 15.5%, and 15.2% in corresponding age groups, p < 0.003), and late mortality (0.6%, 1%, 1.5%, 4.3%, and 9.8%, respectively, p < 0.01). However, early return of angina was lower (2.6%, 1%, 0.8%, 0.9%, and 0%, p < 0.06). CONCLUSIONS: This retrospective, nonrandomized study suggests that older age is not a risk factor for operative mortality in patients undergoing coronary artery bypass grafting with double skeletonized internal thoracic arteries. Apart from avoiding morbidity associated with leg incisions, older patients showed an interesting trend toward lower rates of angina return. Older patients, however, sustained increased perioperative morbidity and late mortality rates.

Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia.

OBJECTIVES: The purpose of this study was to explore interactions between paracrine angiotensin II (Ang-II) and tumor necrosis factor-alpha (TNF-alpha) during myocardial ischemia. BACKGROUND: Ischemic myocardium releases significant amounts of TNF-alpha. This paracrine release correlated with postischemic myocardial injury. Other studies showed myocardial protection obtained by the use of angiotensin-converting enzyme inhibitors (i.e., captopril) and the Ang-II type 1 receptor antagonist losartan after ischemia. The possibility that these agents decrease TNF-alpha synthesis has not yet been investigated. METHODS: Using the modified Langendorff model, isolated rat hearts underwent either 90 min of nonischemic perfusion (control group) or 1 h of global cardioplegic ischemia. In both groups, either captopril (360 micromol/liter) or losartan (182.2 micromol/liter) was added before ischemia. The hearts were assayed for messenger ribonucleic acid (mRNA) expression and effluent TNF-alpha levels. In addition, cardiac myocytes were incubated in cell culture with Ang-II. RESULTS: After ischemia, TNF-alpha mRNA expression intensified from 0.63 +/- 0.06 (control group) to 0.92 +/- 0.12 (p < 0.03), and effluent TNF-alpha levels were 711 +/- 154 pg/ml. The TNF-alpha mRNA expression declined to 0.46 +/- 0.07 (p < 0.01) and 0.65 +/- 0.08 (p < 0.02) in captopril- and losartan-treated hearts, respectively. Effluent TNF-alpha was below detectable levels. Concentrations of TNF-alpha in supernatants of incubated cardiac myocytes treated with 10 and 50 nmol/liter of Ang-II were 206.0 +/- 47.0 pg/ml and 810 +/- 130 pg/ml, respectively (p < 0.004). When pretreated with 700 micromol/liter of losartan, TNF-alpha was below detectable levels. CONCLUSIONS: This study presents an original explanation for previously reported myocardial protection after ischemia, obtained by the use of captopril and losartan. These drugs reduce TNF-alpha synthesis, providing strong evidence of active interactions between paracrine TNF-alpha and Ang-II in the evolution of the ischemic cascade.

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.

Emergency myocardial revascularization for acute myocardial infarction: survival benefits of avoiding cardiopulmonary bypass.

OBJECTIVE: Emergency coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI) is associated with increased operative mortality. It has been suggested that this mortality might be reduced by performing the operation without cardiopulmonary bypass (CPB). METHODS: Between January 1992 and April 1998, 77 patients underwent emergency CABG within 48 h of AMI. Thirty seven were operated on with CPB, and 40 without CPB. The two groups were similar regarding age, gender, left-ventricular ejection fraction (EF) and preoperative use of intra-aortic balloon pump (IABP; 50%). The mean number of grafts/patient was 3 in the CPB group, and 1.9 in the No-CPB group (P<0.0001). RESULTS: Operative mortality in the CPB group was 24% (nine of 37) compared to 5% (two of 40) without CPB (P=0.015). Follow-up ranged between 6 and 66 months. There were no late deaths in the CPB group compared to nine (22%) in the No-CPB group (P<0.0066). Patients operated on with CPB had lower rates of recurrent angina (0 versus 15%; P=0.04) and re-interventions (0 versus 15%; P=0.04). CONCLUSIONS: Our experience suggests that CABG without CPB is the preferred method of myocardial revascularization, due to the fact that it carries lower mortality than CABG with CPB. The trade-off includes increased rates of recurrent angina, re-interventions and late mortality.

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.

Protamine induces vasorelaxation of human internal thoracic artery by endothelial NO-synthase pathway.

BACKGROUND: Protamine is commonly used in cardiac surgery to reverse the anticoagulant effects of heparin. We investigated the role of different nitric oxide synthase pathways in the response of the human internal thoracic artery to protamine and evaluated whether heparin could prevent this effect. METHODS: A tension-recording method was used to obtain baseline measurements of contractions of human internal thoracic artery rings achieved with norepinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as control. The other contained a heparin or Nomega-Nitro-L-arginine (L-NAM, an inhibitor of both endothelial and inducible nitric oxide synthase) or a specific inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasing doses of protamine were added to both chambers and dose-response curves were obtained. RESULTS: Protamine was found to relax contracted internal thoracic arteries 56% +/- 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presence of aminoguanidine or heparin. CONCLUSIONS: Protamine induces nitric oxide-dependent relaxation of the internal thoracic artery by activation of endothelial nitric oxide synthase pathway. Heparin could not prevent this relaxing effect of protamine.

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.

Dissociation between the state of leukocyte adhesiveness/aggregation in the peripheral blood and the availability of the CD11B/CD18 and CD62L antigens on the surface of the cells in patients with stress.

We adopted whole blood flow cytometry and direct labeling of the CD11b/CD18 and the CD62L antigens to study the relationship between their expression on the surface of peripheral leukocytes and the state of leukocyte adhesiveness/aggregation (LAA) as revealed by the leukergy test. We examined patients with infection/inflammation, acute stress and controls. The mean +/- S.D. channel fluorescence intensity of CD11b/CD18 antigen did not differ between patients with infection/inflammation (173 +/- 78) and controls (167 +/- 72). However, a significant (p < 0.0001) difference between these groups was noted regarding LAA state. There was a significant (p = 0.04) reduction in CD11b/CD18 in stress (135 +/- 60) and a significant (p < 0.001) increment in LAA. In both study groups, there was a significant reduction in CD62L. Patients were divided into those with CD11b/CD18 above and below the control's average. No correlation was found between the antigens and LAA. We assume that LAA in patients with stress state is CD11b/CD18 and CD62L independent.

[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.

Captopril in cardioplegia and reperfusion: protective effects on the ischemic heart.

BACKGROUND: Previous studies have shown that long-term treatment with the angiotensin-converting enzyme inhibitor captopril attenuates left ventricular dilatation and improves survival after extensive myocardial infarction. However, there is only sparse evidence of the immediate effects of the drug on hearts undergoing global ischemia and reperfusion. The purpose of this study was to investigate the direct effect of captopril, given in cardioplegia or after ischemia, on the functional recovery of the reperfused myocardium. METHODS: Isolated rat hearts undergoing warm cardioplegic arrest followed by 1 hour of global ischemia and 30 minutes of reperfusion were studied using the modified Langendorff model. RESULTS: After ischemia, hearts receiving captopril (360 mumol/L) either in the cardioplegic solution (n = 9) or during reperfusion (n = 9) developed higher pressure (p < 0.001), greater first derivative of the rise in left ventricular pressure (p < 0.01 and p < 0.001, respectively), greater first derivative of the fall in left ventricular pressure (p < 0.001 and p < 0.002), higher pressure-time integral (p < 0.001), greater coronary flow (p < 0.001), and higher oxygen consumption values (p < 0.001 and p < 0.003) compared with the control group (n = 9). Hearts receiving captopril both in the cardioplegia and during reperfusion (n = 9) had the best recovery of all three groups and lower levels of creatine kinase (47.8 +/- 5.9 U/L versus 73.3 +/- 5.6 U/L; p < 0.01) compared with the control group. CONCLUSIONS: Captopril given in cardioplegia and in reperfusion has a favorable, protective, and additive effect on the recovery of isolated rat hearts undergoing global ischemia and reperfusion; hemodynamic performance improves, coronary flow and oxygen consumption increase, and myocardial damage decreases.