The direct determinants of coronary flow are lumen area and blood flow velocity; however, the precise mechanisms that control these factors are not fully understood. The aim of the present study was to assess by which mechanisms lumen area and coronary flow velocity interact with hemodynamic and morphometric factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound measurements were performed in 28 patients without coronary lumen irregularities. Flow velocity and lumen cross-sectional area were measured in the proximal segments of all three coronary arteries. Global lumen cross-sectional area and global flow were obtained by adding up the values of all three coronary arteries. Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate and pressure-rate products reflecting myocardial oxygen demand were calculated. Global coronary flow increased during adenosine-induced hyperemia from 197 +/- 72 to 637 +/- 204 ml/min (P < 0.001). Global coronary flow closely correlated with the stress-mass-heart rate product (r = 0.62; P < 0.001). Looking at the two constituents of flow separately, global coronary cross-sectional area was closely related to left ventricular muscle mass (r = 0.61; P < 0.001), whereas mean coronary flow velocity at rest showed a strong linear relation with the pressure-rate product (r = 0.64; P < 0.001). There was no interaction between cross-sectional area and blood flow velocity in any of the coronary vessels. Coronary lumen size and flow velocity, the two determinants of coronary flow, are principally determined by different physiological factors. Long-term flow adaptation is achieved by an increase in coronary lumen size, whereas short-term myocardial oxygen requirements are met by changes in resting flow velocity.

The 894T allele of a G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene is associated with decreased eNOS activity, cleavage of the protein, and endothelial dysfunction. The present study evaluated the association with coronary blood flow (CBF) at rest and during adenosine (ADO)-induced hyperemia. CBF was determined by Doppler flow wire and angiography in 97 left anterior descending arteries of individuals without coronary artery disease. At rest, average peak velocity (APV) was lower and coronary vascular resistance (CVR) was higher in homozygous carriers of the 894T allele than in heterozygotes and individuals without the 894T allele. CBF tended to be lower in eNOS 894T allele carriers. During ADO-induced hyperemia (18 microg ic), APV, CVR, and CBF were not statistically different between the genotypes. The reduced APV at rest in conjunction with an increased CVR indicates a vasomotor dysfunction related to an increased microvascular resting tone in eNOS 894T allele carriers.

1 We have compared the signalling mechanisms involved in the pertussis toxin-sensitive and -insensitive contraction of rat isolated mesenteric microvessels elicited by sphingosylphosphorylcholine (SPC) and noradrenaline (NA), respectively. 2 The phospholipase D inhibitor butan-1-ol (0.3%), the store-operated Ca 2+ channel inhibitor SK&F 96,365 (10 mM), the tyrosine kinase inhibitor genistein (10 mM), and the src inhibitor PP2 (10 mM) as well as the negative controls (0.3% butan-2-ol and 10 mM diadzein and PP3) had only little e ect against either agonist. 3 Inhibitors of phosphatidylinositol-3-kinase (wortmannin and LY 294,002, 10 mM each) or of mitogen-activated protein kinase kinase (PD 98,059 and U 126, 10 mM each) did not consistently attenuate NA-and SPC-induced contraction as compared to their vehicles or negative controls (LY 303,511 or U 124). 4 The phospholipase C inhibitor U 73,122 (10 mM) markedly inhibited the SPC-and NA-induced contraction (70% and 88% inhibition of the response to the highest NA and SPC concentration, respectively), whereas its negative control U 73,343 (10 mM) caused only less than 30% inhibition. 5 The rho-kinase inhibitors Y 27,632 (10 mM) and fasudil (30 mM) caused a rightward-shift of the NA concentration-response curve by 0.7 ± 0.8 log units and reduced the response to 10 mM SPC by 88% and 83%, respectively. 6 These data suggest that SPC and NA, while acting on di erent receptors coupling to di erent G-protein classes, elicit contraction of rat mesenteric microvessels by similar signalling pathways including phospholipase C and rho-kinase.

The concept of CFVRcorr standardizes CFVR for bAPV and age as the major physiological determinants. Especially in patients with microvascular dysfunction, this approach may help to discriminate between conditions directly affecting vasodilator reserve and conditions primarily affecting bAPV.

The 825T allele of a common C825T polymorphism in the gene encoding the L L3 subunit of heterotrimeric G proteins is associated with enhanced activation of pertussis toxin (PTX)-sensitive G proteins. We investigated responses of human platelets upon stimulation with epinephrine, which activates PTX-sensitive G proteins, and with agonists which activate additionally, or exclusively PTX-insensitive pathways. Slopes and maximum of the secondary aggregation were significantly enhanced in platelets from 825T allele carriers after epinephrine, and after combined epinephrine/ADP. This effect was more pronounced after inhibition of the cyclooxygenase-2 pathway by acetylsalicylic acid. This phenomenon appeared independent of platelet secretion, or inhibition of the adenylyl cyclase. ß

No abstract

1 The lysophospholipids, lysophosphatidic acid and sphingosine 1-phosphate, have been reported to activate platelets. Here we examined e ects of the naturally occurring related sphingosylphosphorylcholine (SPC) on human platelet function. 2 Platelet activation was determined as aggregation, elevation of intracellular Ca 2+ concentrations, surface expression of P-selectin, GP 53, and GP IIb/IIIa neoepitope PAC-1, and of ®brinogen binding to the platelet surface. 3 Platelets were activated by ADP (5 and 20 mM), the thrombin receptor-activating peptide TRAP-6 (5 and 20 mM), the thromboxane A 2 mimetic U-46619 (1 mM) and collagen (20 and 50 mg ml 71 ) but not by SPC (up to 20 mM). 4 SPC concentration-dependently (IC 50 approximately 1 ± 10 mM) inhibited activation of washed human platelets in response to all of the above agonists, with almost complete inhibition occurring at 20 mM SPC. 5 The SPC stereoisomers, D-erythro SPC and L-threo SPC, exhibited similar concentration ± response curves in inhibiting 20 mM ADP-induced platelet aggregation, suggesting that SPC did not act via speci®c lysophospholipid receptors. 6 Although SPC slightly activated platelet protein kinase A (as assessed by VASP phosphorylation), this e ect could not explain the marked platelet inhibition. Possible protein kinase C inhibition also did not explain the inhibition of platelet activation by SPC. On the other hand, SPC suppressed agonist-induced Ca 2+ mobilization and phospholipase C stimulation. 7 These results indicate that the lysophospholipid SPC is an e ective inhibitor of human platelet activation, apparently primarily by uncoupling agonist-activated receptors from their e ectors.

Coating stents with autologous venous grafts has been suggested to prevent problems associated with conventional stenting, but the need for surgical vessel harvest hampered broad application. A novel synthetic coronary stent graft (CSG) overcomes this limitation by a synthetic membrane, fixed between two thin metallic stents. We successfully implanted 21 CSGs in 18 patients for treatment of acute coronary rupture, thrombus‐containing lesions, and lesions with plaque rupture or adjacent pseudoaneurysm. Substantial residual angiographic diameter stenoses were seen in seven CSGs (25% ± 10% vs. 8% ± 6%; P < 0.01), which were implanted with relatively small balloon catheters (balloon‐to‐artery ratio 1.00 ± 0.09 vs. 1.24 ± 0.18; P = 0.01) and required postdilatation. Overall, the largest balloon catheter applied measured 4.0 ± 0.7 mm (balloon‐to‐artery ratio 1.21 ± 0.20) and the inflation pressure was 16 ± 3 atm. Final intravascular ultrasound imaging demonstrated adequate and symmetrical expansion of the CSG (≥85% ± 15% of the reference lumen). Elective implantation was associated with two small non–Q‐wave myocardial infarctions, resulting from unavoidable occlusions of side branches. Thus, implantation of CSG is feasible and safe. Adequate expansion can be achieved by the use of relatively large low‐compliant balloon catheters inflated with high pressure. Cathet. Cardiovasc. Intervent. 47:496–503, 1999. © 1999 Wiley‐Liss, Inc.