The risk factors for radial artery and saphenous vein graft occlusion are different.

Objectives. To determine risk factors for radial artery and saphenous vein graft occlusion during long-term follow-up after coronary artery bypass grafting (CABG). Methods: From a cohort of 119 patients who had received a radial artery graft, 76 - of whom 55 also had at least one saphenous vein graft - underwent a preplanned direct angiography and anthropometric, biochemical, and endothelial function assessment 7.6-12.1 (mean 8.9) years after CABG. Comorbidity, medication, and smoking habits were also recorded. The association between these parameters and conduit longevity was analyzed in univariable and multivariable logistic regression models. Results: Radial artery graft occlusions were associated with higher plasma levels of high-sensitive C-reactive protein and patency was best among patients with pharmacologically treated hypertension. The sole independent risk factor identified for saphenous vein graft occlusion was tobacco smoking 8-12 years postoperatively. Conclusion: Our data support the contention that the pathogenesis of radial artery graft failure is distinct from vein graft disease and is related to hypertension status and systemic inflammation. These risk factors are potential targets for preventive measures. Accordingly, the study supports the eventual design of personalized secondary prevention regimens.Clinical registration number: ISRCTN23118170.

Direct angiography demonstrates equal 8-12 years patency rates of radial artery and saphenous vein grafts.

Objectives: The benefits of coronary artery bypass surgery depend on lasting graft patency. To aid rational graft selection, the relative long-term merits of radial artery and saphenous vein grafts need to be determined by a gold standard method and with minimal clinically driven selection bias. Methods: The patency rates of various conduits were determined by direct angiography in 76 patients from a cohort of 119 undergoing coronary artery bypass grafting 7.6-12.1 (mean 8.9) years before. Results: 14 out of 76 radial artery and 10 out of 61 saphenous vein grafts were occluded (rates 0.18 and 0.16, respectively). Conclusion: The high long-term patency rate of saphenous vein grafts does not support a preferential use of the radial artery as a coronary artery bypass conduit. Clinical registration number: ISRCTN23118170.

Arterial grafts do not counteract target vessel occlusion.

OBJECTIVES: Grafted, non-occluded coronary arteries might contribute substantially to the myocardial blood supply and serve as a basis for vascular collateralization which preserves the myocardium in the event of graft occlusion. Early studies indicated that grafting with saphenous vein, but not internal mammary arteries, accelerates coronary atherosclerosis. This has not been extensively studied for the radial artery, which like the internal mammary artery (IMA) is largely resistant to atherosclerosis. A differential effect of various grafts might facilitate identification of disease-modifying principles. Our surgical cohort represented an opportunity to analyse new native coronary occlusions by comparison with preoperative angiograms. METHODS: One hundred and two patients underwent angiography 1.3-3.9 years after coronary artery bypass surgery, primarily in order to compare the patency of radial artery, IMA and saphenous vein grafts. RESULTS: Out of 290 stenotic, grafted vessels, 67 (23%) occluded during follow-up. Native occlusion occurred in 47% of the patients and correlated with serum-cholesterol. In a per target analysis, independent predictors of postoperative native occlusion were the right coronary artery territory, patent corresponding graft, the corresponding graft being an IMA and end-to-side anastomosis. CONCLUSIONS: Target vessel occlusion is similar with radial artery and saphenous vein grafts and proceeds rapidly even in the current era of secondary prophylaxis against atherosclerosis. Competitive graft flow appears to promote occlusion. Contrary to previous studies, we do not find vein grafts to be inferior to IMA grafts with respect to preservation of native vessel patency.

Radial artery graft patency relates to gender, diabetes mellitus and angiotensin inhibition.

UNLABELLED: The radial artery is resistant to atherosclerotic degeneration and therefore appears more attractive for coronary artery bypass grafting than the saphenous vein. However, the patency of radial artery grafts varies widely among studies. Therefore, before deciding whether to adopt this as the conduit of choice second to internal mammary artery grafts, we have prospectively monitored our first cohort of patients with radial-to-coronary bypasses. DESIGN: Angiographic and clinical outcome parameters were registered for the 119 patients receiving radial artery grafts at our institution during April 4, 2001 to October 7, 2003. RESULTS: Reangiography of 102 patients (86%) showed that after two to three years, 79% of the radial artery and 87% of the saphenous vein grafts remained patent. Radial artery harvesting was well tolerated. Patency of radial artery grafts was correlated to diabetes mellitus (detrimental), gender (women had higher occlusion rates), and use of angiotensin inhibiting medication (beneficial). CONCLUSIONS: The pre-study assumption that radial artery grafts would out-perform those of saphenous vein at mid-term is not borne out. The propensity of radial artery graft failure in diabetics and the higher patency associated with angiotensin inhibition might both relate to endothelial modulation of the muscular tone of the graft.

Adenosine protects against hypoxic injury at hypothermia in guinea pig papillary muscles.

OBJECTIVES: To investigate the protective effects of adenosine against hypoxic injury at hypothermia; both magnitude and mechanisms. DESIGN: Receptor versus non-receptor dependent mechanisms in cardioprotection by adenosine were examined in guinea pig papillary muscles exposed to glucose free hypoxia at 24 degrees C. Contractile force amplitude (CFA) and action potential duration (APD) during increasing concentrations of adenosine at 37 degrees C, 30 degrees C and 24 degrees C normoxia were also examined. RESULTS: CFA was significantly improved after adenosine treatment during hypothermic hypoxia compared to control (80.7+/-17.4% vs 40.5+/-10.7%, p<0.001). Adenosine receptor antagonist SPT did not antagonize (64.6+/-21.1%), and adenosine receptor agonists (APNEA+NECA) could not mimic the cardioprotection (53.8+/-9.3%). MitoK(Ca) blocker paxilline antagonized the cardioprotection (40.0+/-7.7%). During normoxic conditions hypothermia-induced increase in CFA was significantly decreased by adenosine (0.12-12 mM) whereas the increase in action potential duration was potentiated. CONCLUSION: Adenosine (1.2 mM) had marked cardioprotective effect in hypothermic substrate free hypoxia. Possible mechanisms are non-receptor dependent and related to mitoK(Ca) channels. The cardiodepressive effect at hypothermia may contribute to cardioplegia.

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation.

OBJECTIVE: We have recently shown that adenosine instead of supranormal potassium in cold crystalloid cardioplegia improves cardioprotection. Studies indicate that hyperkalemia has unfavorable effects on vascular endothelial function. Three pathways have been identified as major vasodilatory pathways: the nitric oxide (NO) pathway, the cyclooxygenase (COX) pathway, and the endothelium-derived hyperpolarization (EDHF) pathway, where the EDHF pathway, in particular, seems susceptible to hyperkalemia. We hypothesized that adenosine cardioplegia improves postcardioplegic endothelial function. METHODS: Sixteen pigs were randomized to receive either cold (6 degrees C) hyperkalemic cardioplegia (n=8) or cardioplegia where hyperkalemia was substituted with 1.2 mM adenosine (n=8). After 1h of cold ischemic arrest, coronary blood flow was monitored for the following 2h. The LAD artery was then explanted, and cylindrical rings were mounted for isometric tension recordings in organ chambers. Vessels were preconstricted with U46610 (Thromboxane A(2) analog) and then bradykinin-mediated relaxation was investigated. To differentiate between the vasodilatory pathways the relaxation was assessed in the absence and presence of inhibitors of the COX (indomethacin), NO (L-NAME+carboxy-PTIO), and EDHF (apamin+charybdotoxin) pathways. RESULTS: Invivo: The adenosine group had, as distinct from the hyperkalemic group, a significantly increased coronary blood flow index 1h after cross-clamp release (from (ml/min/100 g, mean+/-SD) 50.9+/-13.9 to 72.8+/-21.9, p=0.010). The difference was, however, not statistically significant between groups. Invitro: Maximal relaxation without blockers was 27.4+/-10.1% of maximal tension in the adenosine group and 22.2+/-7.5% in the hyperkalemic group. To investigate EDHF-dependent vasodilation the vessel rings were simultaneously treated with indomethacin, L-NAME, and carboxy-PTIO. Maximal relaxation in the hyperkalemic group was then reduced to 47.4+/-17.4% of maximal tension, which was a significant reduction compared to the adenosine group with a maximal relaxation of 20.6+/-8.7% (p=0.028). CONCLUSION: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow and preserves EDHF-dependent vasodilation.

Adenosine instead of supranormal potassium in cardioplegic solution improves cardioprotection.

OBJECTIVE: To determine whether adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest and improved cardioprotection. Cold crystalloid cardioplegia with adenosine, procaine and magnesium (A) was compared with standard cold crystalloid hyperkalemic cardioplegia (K). METHODS: Sixteen pigs were randomized to receive either cold K (n=8) or A (n=8), where hyperkalemia was substituted with 1.2 mM adenosine. The cold (6 degrees C) cardioplegia was given intermittently and antegradely, with an aortic cross-clamp time of 1 h. Hemodynamic data was continuously measured and pressure-volume conductance catheters were used to determine global left ventricular systolic and diastolic function. Coronary flow and O2 content differences allowed determination of left ventricular energetics. Blood samples, and left ventricular microdialysis were used to measure parameters of ischemia. Measurements were done at 1 and 2 h after cross-clamp release. RESULTS: Mean arterial pressure was reduced with 55 mmHg (standard deviation, SD: 19) in the K group versus 30 mmHg (SD: 14) in the A group 2 h after cross-clamp release (p=0.030). Left ventricular contractility expressed as slope of the preload recruitable stroke work index (Mw) was reduced to 53% (SD: 14) in the K group versus 78% (SD: 23) in the A group 2h after cross-clamp release (p=0.046). Reduction of maximum of first derivate of pressure with respect to time (dP/dtmax) was 804 mmHg/s (SD: 189) in the K group versus 538 mmHg/s (SD: 184) in the A group (p=0.033). The slope of the myocardial oxygen consumption-pressure volume area was at 2 h reperfusion increased from 1.37 (SD: 0.64) to 2.86 (SD: 1.27) in the K group, whereas no shift was detected in the A group (p=0.019). Cardiac troponin T measured in the coronary sinus 1 h after cross-clamp release was 1.25 microg/l (SD: 0.64) in the K group versus 0.73 microg/l (SD: 0.31) in the A group (p=0.046). CONCLUSION: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest, improves post cardioplegic left ventricular systolic function and efficiency, and attenuates myocardial cell damage.

Contractile recovery of heart muscle after hypothermic hypoxia is improved by nicorandil via mitochondrial K(ATP) channels.

BACKGROUND: The ATP-sensitive potassium channel (K(ATP)) opener nicorandil used instead of potassium in hypothermic cardioplegia significantly improves preservation of cardiac function and energetics in the in situ heart preparation. The present study, therefore, examines the effect of nicorandil at different temperatures and the role of sarcolemmal and mitochondrial K(ATP) channels under ex vivo conditions using contractile force (CF) and action potential duration (APD) as end points. METHODS: Guinea-pig papillary muscles at 37, 27, or 22 degrees C (1Hz) were exposed to nicorandil 0.2-1.1 mM. The contributions of K(ATP) channel subtypes in cardioprotection were examined using mitochondrial (mito) (0.1 mM) or non-selective (1.0 mM) concentrations of nicorandil, mito K(ATP) blocker 5-hydroxyl decanoate (5HD, 300 microM) or sarcolemmal (sarc) K(ATP) blocker HMR1098 (30 microM) before and during 140 min of hypothermic (22 degrees C) glucose-free hypoxia. RESULTS: Nicorandil >0.5 mM shortened the APD, and this was abolished by hypothermia and HMR1098 but not by 5HD. Nicorandil in both tested concentrations preserved contractile force after hypoxia-reoxygenation significantly better than control (73.7+/-4.4% and 75.8+/-3.9% vs 40.6+/-2.6%, n=6 in each group). Protection was blocked by 5HD but not by HMR1098. 5HD and HMR1098 alone did not change recovery of contractile force compared to control. CONCLUSION: Shortening of APD and activation of sarc K(ATP) by nicorandil were not related to myocardial protection. Thus, the mito K(ATP) seems to play a significant role in cardioprotection compared to the sarc K(ATP) also when substrate depletion and hypoxia are combined with hypothermia.

Clinical testing of nicorandil supplemented normokalemic cardioplegic solution.

Does nicorandil instead of supranormal potassium safely provide cardioplegia and cardioprotection in humans? Fifty patients eligible for coronary artery surgery were randomly divided into two groups; one group received standard St Thomas' Hospital solution (STHS) and the other group got a crystalloid solution in which supranormal potassium was replaced with 0.2 mmol/l nicorandil. We measured time to arrest, rhythm abnormalities, pre- and postoperative troponin-T, CK-MB and myoglobin release as well as hemodynamic parameters. Time to arrest was significantly shorter in the STHS group (41.0+/-16.8 s) than in the nicorandil group (120.9+/-78.8 s, P<0.001). Four patients in the nicorandil group needed additional STHS to achieve satisfactory cardiac arrest. Troponin-T was elevated in the nicorandil group at four (P=0.042) and at eight (P=0.044) hours after surgery, myoglobin levels were elevated at 0 h after surgery (P=0.014), CK-MB levels were not group different. Hemodynamic performance was similar in both groups. Potassium should probably not be replaced by nicorandil alone in the cardioplegic solution. This study of low-risk patients with short (43.2 min) aortic cross-clamp times showed similar cardioprotection as revealed by hemodynamic performance whereas early release of troponin-T and myoglobin release in the nicorandil group raised some concern.

Replacing potassium with nicorandil in cold St. Thomas' Hospital cardioplegia improves preservation of energetics and function in pig hearts.

BACKGROUND: To determine whether the adenosine triphosphate-sensitive potassium channel opener nicorandil, instead of potassium in cold crystalloid cardioplegia, may enhance cardioprotection, crystalloid cardioplegia with nicorandil, magnesium, and procaine was compared with standard crystalloid cardioplegia in terms of left ventricular performance and efficiency. METHODS: Sixteen pigs were randomly assigned to receive cold hyperkalemic crystalloid cardioplegia (n = 8) or nicorandil in cold saline (n = 8). Cold (4 degrees C) cardioplegic solutions were given antegradely and intermittently, with a cross-clamp time of 60 minutes. The preload recruitable stroke work relationship (PRSW), pressure-volume area (PVA), and myocardial oxygen consumption (MVO(2)) were calculated at baseline and at one and two hours following cross-clamp release, using combined pressure-volume conductance catheters, coronary flow probes, and O(2)-content differences. RESULTS: The left ventricular contractility expressed in PRSW was reduced to 58% (standard deviation [SD]: 20) of baseline in the crystalloid group and to 89% (SD: 20) in the nicorandil group two hours after cross-clamp release (p = 0.044). The slope of the MVO(2)-PVA relationship increased in the crystalloid group from 1.59 (SD: 0.22) before cardioplegia to 2.55 (SD: 0.73) afterwards, significantly more than in the nicorandil group, where the slope changed from 1.69 (SD: 0.30) to 1.95 (SD: 0.47) (p = 0.027). CONCLUSIONS: Nicorandil in a crystalloid cardioplegic solution was easily employed and contractility was significantly better than after standard hyperkalemic cardioplegia. The smaller shift of the slope in the MVO(2)-PVA relationship in the nicorandil group shows improved efficiency in oxygen to mechanical transfer compared with the crystalloid group.