The Clinical And Experimental Study In Coronary Slow Flow

Coronary slow flow(CSF) phenomenon is an angiographic observation characterized by delayed opacification of the distal vasculature in the absence of obstructive coronary disease. This angiographic finding showing slow contrast progression was first described in six patients with typical angina pectoris by Tambe et al. And there are just a few studies reported about the etiology of this phenomenon since then. Although the knowledge concerning the etiopathogenesis of CSF is scarce, coronary microvascular endothelial dysfunction and increased microvascular resistance are thought to play important roles. The elevated homocysteine (Hcy) level has been reported to be associated with endothelial dysfunction and contributes to increased risk of cardiovascular disease regardless of conventional risk factors.The mechanisms mediating Hcy-induced vascular changes are not completely defined. On exercise myocardial perfusion scintigraphy, reversible perfusion defect (RPD) can also be detected in some of these patients. The exact mechanism of the perfusion changes in these patients is not understood very well. So we made this clinical and experimental study in order to investigate the pathophysiological and its mechanisms of CSF, so as to provide assistance for clinical analysis, disease risk assessment and treatment.Objective1. To investigate the relationship between CSF phenomenon and myocardial ischemia through adenosine myocardial perfusion single-photon emission computed tomography(SPECT)2. To probe the mechanism of CSF by observing the changes of plasma Hcy , the nitric oxide (NO) production and NO synthase (NOS) activity in plateletsMethods1. Patients who were hospitalized with the compain of chest pain, therefore underwent coronary angiography(CAG) and adenosine myocardial perfusion SPECT from April 2006 to December 2007 were enrolled in this study. The patients were divided into 3 groups according to their coronary angiography results, i.e. twenty-five patients in CSF group, 20 patients in normal coronary flow(NCF) group and 20 in the coronary artery stenosis group.2. Coronary flow patterns of the cases were determined by corrected thrombolysis in myocardial infarction (TIMI) frame count(CTFC) method. 3. CAG, electrocardiograph(ECG) and adenosine myocardial perfusion SPECT were performed in all patients.4. The change of platelet count(PC), mean platelet volume(MPV), platelet distribution width(PDW), plasma Hcy, the NO production and NOS activity in platelets were measured.Results1. Patients with CSF revealed both higher frame counts in native coronary arteries and higher mean frame counts than NCF. The coronary mean frame count was 30.71±5.00 in patients with CSF and 18.75±3.35 in NCF patients, respectively (P<0.001).2. Patients who had positive rest ECG in coronary artery stenosis were significantly increased than in CSF and NCF groups(70%, 20%, 10%, respectively, P<0.05). But the CSF and NCF group that had no difference in rest ECG (20% vs 10%, P>0.05). The positive rate of adenosine stress ECG was coronary artery stenosis group > CSF > NCF pattern(85%, 52%, 20%, respectively, P<0.05). 90% cases with coronary artery stenosis had positive adenosine myocardial perfusion SPECT, which showed no significant difference with CSF(90% vs 84%, P>0.05). But these two groups were significantly increased than NCF (90%, 84% vs 25%, P<0.05).3. The reversible perfusion defect (RPD) on the adenosine myocardialperfusion SPECT of CSF was significantly higher than positive of adenosine stress ECG(84% vs 52%, P<0.05) and rest ECG(84% vs 20%, P<0.05).4. Adenosine myocardial perfusion SPECT showed the scope of myocardial ischemia in NCF, CSF and coronary artery stenosis group were 0.65±1.23. 2.72±1.93, 4.50±4.11. And the degree of myocardial ischemia in these three groups were 1.10±2.02, 6.31±5.54, 11.8±14.01. The scope and degree of myocardial ischemia on adenosine myocardial perfusion SPECT was coronary artery stenosis group > CSF > NCF pattern(P<0.01).5. The incidence rate of CSF in LAD, LCX and RCA had no significant difference (35%, 33%, 31 %, respectively, P>0.05).6. The positive coincidence rate of adenosine myocardial perfusion SPECT in single-vessel and double-vessel group was higher than adenosine stress ECG (82%, 100% vs 45%, 20%), but was similar with adenosine stress ECG in the triple-vessel group (78%).7. PC, MPV, PDW had no significant differences in the three groups (P>0.05). 8. The platelets NO(umol/gprot) production in CSF was lower by 69% (0.40±0.33 vs 1.27±0.80, P<0.01) than that in NCF, and lower by 39%(0.40±0.33 vs 0.66±0.40, P<0.05) than that in coronary artery stenosis group. The activity of platelets NOS(U/mgprot) in CSF was lower by 22%(1.69±0.15 vs 2.17±0.21, P<0.01) than that in NCF, and lower by 11%( 1.69±0.15 vs 1.90±0.27, P<0.01) than coronary artery stenosis group.9. Plasma Hcy level(umol/L) was significantly higher in patients with CSFthan in the NCF (18.40±6.26 vs 11.25±4.26, p<0.01), and higher than coronary artery stenosis group(18.40±6.26 vs 14.53±4.47, P<0.05).10. The production of NO and the activity of NOS in platelets had negative correlation with plasma Hcy level (r = -0.52, P = 0.000; r = -0.42, P = 0.001, respectively).Conclusions1. There was a possible close relationship between coronary slow flow phenomenon and myocardial ischemia. Adenosine stress SPECT could discover this myocardial ischemia in CSF. The scope and degree of myocardial ischemia on adenosine myocardial perfusion SPECT was coronary artery stenosis group > CSF > NCF pattern.2. The positive coincidence rate of adenosine myocardial perfusion SPECT in CSF was significantly higher than that of adenosine stress ECG and rest ECG.3. Adenosine myocardial perfusion SPECT was considered as an useful non-interventional method for detecting CSF patient's myocardial ischemia, providing assistance for clinical analysis, disease risk assessment and treatment.4. In CSF group the production of NO and the activity of NOS in plateletswere obviously lower than that in NCF and coronary artery stenosis group. Plasma Hcy level of patients with CSF was found to be significantly higher than that in NCF and coronary artery stenosis groups.5. The production of NO and the activity of NOS in platelets had negative correlation with plasma Hcy level.6. The impaired endothelial cell function caused by the elevated Hcy mightbe related to the decrease of the bioavailability of NO by reducing its synthesis, which might play a role in the pathogenesis of CSF.