Structural myocardial changes after coronary artery surgery.

BACKGROUND: Postoperative contractile dysfunction or 'myocardial stunning' has been described after coronary artery bypass grafting (CABG). In the present study we sought to determine if and to what extent clinical, structural and histochemical evidence of myocardial changes associated with stunning could be found in patients after CABG and cold crystalloid cardioplegia. MATERIALS AND METHODS: Left ventricular (LV) biopsies were obtained from CABG patients (n = 10) prior to and at the end of cardiopulmonary bypass (CPB). These biopsies were immunostained for the inducible heat-shock protein 70 (HSP-70i), intercellular adhesion molecule-1 (ICAM-1) and actin. ATP was measured by bioluminescence. RESULTS: Biopsies pre-CPB showed no evidence of myocardial damage as HSP-70i was absent and a regular actin cross-striation pattern and only constitutive ICAM-1-expression were present. After CPB we found significantly increased HSP-70i and ICAM-1 levels as well as a deranged actin cross-striation pattern with a widening of actin bands. ATP levels declined from 10 mmol L-1 pre-CPB to 4.9 mmol L-1 after CPB. Correspondingly, coronary sinus effluent showed a significant lactate production. Although, cardiac function determined by transoesophageal echocardiography did not deteriorate, significant inotropic support was necessary to maintain cardiac output. CONCLUSIONS: Our results present clinical and structural evidence of 'myocardial stunning' after CABG and cold crystalloid cardioplegia. Increased HSP-70i and ICAM-1 expression, as well as a deranged actin cross-striation pattern, might be structural markers to determine 'myocardial stunning' in clinical settings.

Activation of myocardial constitutive nitric oxide synthase during coronary artery surgery.

OBJECTIVE: The role of nitric oxide (NO) in myocardial ischemia/reperfusion is controversial. While some studies have shown cardioprotective effects of NO, others suggested that increased myocardial NO release secondary to ischemia may contribute to reperfusion injury. However, the impact of cardioplegia-induced myocardial ischemia/reperfusion on the activity of the NO-producing enzyme constitutive NO-synthase (cNOS or NOS-III) has not been investigated. METHODS: Twenty elective CABG patients were randomized to receive myocardial protection using either intermittent cold blood cardioplegia with 'hot-shot' (CBC; n=10) or continuous warm blood enriched with the ultra-fast-acting beta-blocker esmolol (WBE; n=10). We collected transmural LV biopsies prior to cardiopulmonary bypass (CPB), at the end of the cross-clamp period, and at the end of CPB. Specimen were subjected to immunocytochemical staining against myocardial NOS-III and cGMP using polyclonal antibodies. NOS-III activity was determined using TV-densitometry (gray units) and cGMP content using a semiquantitative score. Global myocardial metabolism was assessed by arterio-coronary sinus lactate concentration difference (a-csD(LAC)). For LV function determination we measured the fractional area of contraction (FAC) using TEE. RESULTS: In CBC hearts a-csD(LAC) was significantly decreased following cross-clamp removal as compared to pre-CPB indicating global ischemia during cross-clamp. In contrast, a-csD(LAC) was unchanged in WBE hearts indicating absence of relevant ischemia in this group. In CBC hearts NOS-III activity did not change from pre-CPB (35.6+/-11.1 U) to the end of the cross-clamp period (38. 0+/-8.1 U; P=0.2), but increased significantly to 48.5+/-12.1 U at the end of CPB following initial warm blood reperfusion (P=0.026). In WBE hearts NOS-III activity remained unchanged throughout (29. 2+/-10.8, 35.1+/-11.8, and 32.2+/-14.7 U, respectively; 0.3). At the end of CPB, nine CBC hearts, but only one WBE heart showed increased cGMP content (P=0.002). Compared to pre-CPB, FAC in the CBC group was 109+/-25% following weaning off CPB (P=0.26), but was slightly decreased to 87+/-22% at 4 h post-CPB (P=0.03). In the WBE group FAC remained unchanged compared to pre-CPB throughout (103+/-21 and 96+/-37%, respectively; 0.5). CONCLUSIONS: Our data show that global myocardial ischemia and reperfusion induced by CBC is associated with myocardial NOS-III activation and increased cGMP content suggesting increased NO release. In contrast, avoidance of ischemia by use of WBE prevented NOS-III and c-GMP increase. As LV function was decreased at 4 h post-CPB in the CBC group, these data suggest that increased NO release secondary to NOS-III activation may have contributed to ischemia-reperfusion injury as has been shown experimentally.

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckberg's blood cardioplegia during coronary artery bypass grafting (CABG). METHODS: Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS: There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.