Proefschrift Rijksuniversiteit Groningen. / Datum laatste controle: 15-05-1997. Met bibliogr., lit. opg. - Met een samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Lit.opg. - Samenvatting in het Nederlands.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Note:

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Duits en Nederlands.

The ultimate success of bypass surgery depends on the construction of a technically perfect bypass graft to an appropriate coronary vessel using a conduit which will remain durable for the lifetime of the patient. This thesis explores methods to improve coronary surgery by enhancing intraoperative imaging and conduit selection in the operating room. It is known that technical errors in graft construction cause failure of up to 12% of coronary bypass grafts in the operating room. We performed investigations of a new technique of intraoperative fluorescence angiography using indocyanine green dye to determine graft patency. We developed optimal methods of obtaining images and preliminary investigations revealed the technique was highly reproducible. In a follow-up trial, we demonstrated that over 80% of technical errors which would otherwise have been missed were identifiable with indocyanine green angiography, while only 25% of these errors were identified by transit-time ultrasonic flow measurement, the current clinical standard. We also determine that coronary surgery with indocyanine green angiographic graft patency verification was associated with less perioperative myocardial injury than bypass surgery without graft patency assessment. The long term graft patency of saphenous vein grafts is sub-optimal, with over 40% of such grafts totally occluded and a further 30% significantly diseased at ten years. We attempted to improve these outcomes by increasing the use of arterial grafts, which are less prone to intimal hyperplasia. In a multicentre clinical trial, we demonstrated a 40% relative risk reduction in graft occlusion at one year when radial arteries were used as bypass conduits versus saphenous veins. We identified that women and patients with small coronary vessels maximally benefited from radial artery bypass grafts. Conversely, in settings of less severe target vessel stenosis or concomitant peripheral vascular disease, saphenous veins performed as well as radial arteries. We have demonstrated that high quality imaging to identify technical errors during the operation, increased use of radial artery grafts and careful consideration of individual patient and target vessel characteristics can all improve graft patency. Future studies will be aimed at identifying the role of intraoperative imaging and arterial grafting in improving long-term clinical outcomes.

The ultimate success of bypass surgery depends on the construction of a technically perfect bypass graft to an appropriate coronary vessel using a conduit which will remain durable for the lifetime of the patient. This thesis explores methods to improve coronary surgery by enhancing intraoperative imaging and conduit selection in the operating room. It is known that technical errors in graft construction cause failure of up to 12% of coronary bypass grafts in the operating room. We performed investigations of a new technique of intraoperative fluorescence angiography using indocyanine green dye to determine graft patency. We developed optimal methods of obtaining images and preliminary investigations revealed the technique was highly reproducible. In a follow-up trial, we demonstrated that over 80% of technical errors which would otherwise have been missed were identifiable with indocyanine green angiography, while only 25% of these errors were identified by transit-time ultrasonic flow measurement, the current clinical standard. We also determine that coronary surgery with indocyanine green angiographic graft patency verification was associated with less perioperative myocardial injury than bypass surgery without graft patency assessment. The long term graft patency of saphenous vein grafts is sub-optimal, with over 40% of such grafts totally occluded and a further 30% significantly diseased at ten years. We attempted to improve these outcomes by increasing the use of arterial grafts, which are less prone to intimal hyperplasia. In a multicentre clinical trial, we demonstrated a 40% relative risk reduction in graft occlusion at one year when radial arteries were used as bypass conduits versus saphenous veins. We identified that women and patients with small coronary vessels maximally benefited from radial artery bypass grafts. Conversely, in settings of less severe target vessel stenosis or concomitant peripheral vascular disease, saphenous veins performed as well as radial arteries. We have demonstrated that high quality imaging to identify technical errors during the operation, increased use of radial artery grafts and careful consideration of individual patient and target vessel characteristics can all improve graft patency. Future studies will be aimed at identifying the role of intraoperative imaging and arterial grafting in improving long-term clinical outcomes.

<p>The primary aim of this thesis was to modify saphenous vein (SV) harvesting technique and evaluate its clinical importance. A new "no touch" (NT) technique of SV preparation was developed where the vein is harvested with a pedicle of surrounding tissue, which protects the vein from spasm therefore obviating the need for distension.</p><p>Firstly, a prospective randomised study in 156 patients who underwent coronary artery bypass grafting was done to compare this new "no touch" technique to two others, the conventional (C) and the intermediate (I) techniques. A morphological study of the endothelium showed an endothelial integrity of 97% in NT vessels while about half of endothelial surface of veins harvested by the other two techniques was devoid of endothelium. At angiographic follow up, the patency for NT was 95.4%, 88.9% for grafts in group C and 86.2% for grafts in group I. A statistically significant difference in patency rate was found between the NT group and group C (p=0.025) and the poorest result was observed in group I.</p><p>Secondly, the immunohistochemistry assessment using CD31-antibody confirmed a better-preserved endothelium for NT vessels. Putative NOS was identified by NADPH-diaphorase histochemistry and autoradiographic localization of [3H] L-nitroarginine (NOARG) binding. NADPH staining was almost continuous on the luminal aspect and was also present in the intact adventitia of NT vessels, which was markedly reduced in conventionally harvested veins. Autoradiographic analysis of specific NOARG binding showed greater binding in the no-touch vessels, confirming the histochemistry results. All three NOS isoforms were identified in the media of SV grafts. In NT, NOS I was abundant in adventitial nerves; NOS II was found in adventitial vasa vasorum and NOS III was associated with endothelial cells lining both the vessel lumen and microvessels within the adventitia.</p><p>In conclusion, this study demonstrated that the endothelial integrity and NOS activity are better maintained when using the no-touch technique for vein graft harvesting. The vasorelaxant and thromboresistent activities of NO may be responsible for the reduced venospasm and improved early patency rates observed. Furthermore, the mechanical properties provided by the cushion of surrounding tissue in grafts harvested by NT technique may contribute to the observed high patency rate.</p>

The primary aim of this thesis was to modify saphenous vein (SV) harvesting technique and evaluate its clinical importance. A new "no touch" (NT) technique of SV preparation was developed where the vein is harvested with a pedicle of surrounding tissue, which protects the vein from spasm therefore obviating the need for distension. Firstly, a prospective randomised study in 156 patients who underwent coronary artery bypass grafting was done to compare this new "no touch" technique to two others, the conventional (C) and the intermediate (I) techniques. A morphological study of the endothelium showed an endothelial integrity of 97% in NT vessels while about half of endothelial surface of veins harvested by the other two techniques was devoid of endothelium. At angiographic follow up, the patency for NT was 95.4%, 88.9% for grafts in group C and 86.2% for grafts in group I. A statistically significant difference in patency rate was found between the NT group and group C (p=0.025) and the poorest result was observed in group I. Secondly, the immunohistochemistry assessment using CD31-antibody confirmed a better-preserved endothelium for NT vessels. Putative NOS was identified by NADPH-diaphorase histochemistry and autoradiographic localization of [3H] L-nitroarginine (NOARG) binding. NADPH staining was almost continuous on the luminal aspect and was also present in the intact adventitia of NT vessels, which was markedly reduced in conventionally harvested veins. Autoradiographic analysis of specific NOARG binding showed greater binding in the no-touch vessels, confirming the histochemistry results. All three NOS isoforms were identified in the media of SV grafts. In NT, NOS I was abundant in adventitial nerves; NOS II was found in adventitial vasa vasorum and NOS III was associated with endothelial cells lining both the vessel lumen and microvessels within the adventitia. In conclusion, this study demonstrated that the endothelial integrity and NOS activity are better maintained when using the no-touch technique for vein graft harvesting. The vasorelaxant and thromboresistent activities of NO may be responsible for the reduced venospasm and improved early patency rates observed. Furthermore, the mechanical properties provided by the cushion of surrounding tissue in grafts harvested by NT technique may contribute to the observed high patency rate.