Intracoronary flow velocity or pressure measurements during routine PTCA represent an accurate and, at last, quantitative method for assessing the coronary collateral circulation in humans.
Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and a scavenger of oxygen-derived free radicals. Decreased availability of BH4 leads, under in vitro conditions, to reduced nitric oxide (NO) production and increased superoxide formation. We studied the effect of exogenous BH4 on endothelial function of angiographically normal vessel segments in patients with coronary artery disease. Nineteen patients with coronary artery disease underwent quantitative coronary angiography with simultaneous coronary flow velocity measurements (Cardiometrics FloWire). Data were obtained in angiographically normal segments of the left coronary artery at baseline, after intracoronary (i.c.) administration of acetylcholine (Ach; 10(-4) M), after infusion of BH4 (10(-2) M), and after co-infusion of ACh and BH4. At the end of the study, 300 microg nitroglycerin (NTG) i.c. was administered to obtain maximal vasodilation. At each step, flow velocity was determined before and after 18 microg adenosine i.c. to assess coronary flow velocity reserve. In 15 patients, ACh induced coronary vasoconstriction of -18 +/- 3% (endothelial dysfunction; p < 0.0001 vs. baseline), and in four patients, vasodilation of +39 +/- 20%. In the 15 patients with endothelial dysfunction, BH4 alone did not influence vessel area but prevented vasoconstriction to ACh (+2 +/- 3%, NS, vs. baseline). Correspondingly, calculated volume flow showed the highest value after co-infusion of ACh and BH4. Coronary flow velocity reserve was comparable during the various infusion steps. BH4 prevents ACh-induced vasoconstriction of angiographically normal vessels in patients with coronary artery disease. Thus substitution of this cofactor of NOS may represent a new approach for the treatment of endothelial dysfunction.
Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance.
The purpose of this study was to compare the diagnostic value of MR angiography (MRA) with conventional contrast angiography in coronary artery disease. Thirty-five patients underwent MRA and coronary angiography within 4 hours. Of these, three patients were investigated twice: once before and once after balloon angioplasty. The pulse sequence was a cardiac-triggered, single-slab, three-dimensional gradient-echo sequence, employing a spin-echo navigator echo measurement to track the variation of the diaphragm during the scan. The following segments of the coronary arteries were included in this prospective study: left main coronary artery, proximal and middle left anterior descending, proximal and middle left circumflex, proximal and middle right coronary artery, and intermediate branch, if present. In total, 176 segments were classified as normal or having a stenosis of less than 50% and as having a stenosis of more than 50%. Five patients were excluded because of lack of cooperation. Over all, 45 of 54 stenoses were detected and interpretable by MRA. Sensitivity, specificity, and positive and negative predictive values of MRA for detecting significant stenoses were 83%, 94%, 87%, and 93%, respectively. MRA identified significant stenoses within the major coronary arteries with a high degree of accuracy. Sensitivity and specificity are higher compared with exercise tests or scintigraphy or top of the precise localization.
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