Relationship between coronary collateral growth in the dog and ischemic bed size

Summary Two models of gradual coronary occlusion (Ameroid method) were compared in this study: 3 months circumflex and 3 months right coronary occlusion. Following coronary occlusion, the collaterals developed in intact, normally active dogs. The collateral flows were assessed in an isolated heart preparation. The results indicated a pattern for collateral development. Collateral flow was directed primarily toward the left heart with circumflex occlusion, and toward the right heart with right occlusion. Although dominant collateralization was via epicardial collaterals, intramyocardial septal collaterals strongly participated in growth development of both models. Collateral growth to the circumflex with circumflex occlusion was 6.54 fold greater than collateral growth to the right coronary artery with right occlusion. The data suggest a relationship between collateral growth and ischemic bed size.This work was supported by the American Heart Association, and by USPHS grant HL-24323.     

Coronary collateral circulation

The occurrence and influence of coronary collateral circulation and obstruction of the supplying coronary arteries on left ventricular contractility, prevalence of myocardial infarction, and bicycle exercise ergometer test were studied in a random sample of 286 patients with angiographically documented coronary artery disease. Collaterals appeared increasingly in all three main coronary arteries with grade of obstruction. The highest prevalence of collaterals occurred in stenosis of the right coronary artery (60%), followed by the left descending artery (45%); they occurred least in the left circumflex artery (21%) (p less than 0.001). The frequency of intra-arterial collateral circulation was 42%, 11%, and 12%, respectively (p less than 0.001). With total occlusion of the left anterior descending coronary artery, 22% of the patients had normokinetic anterior and apical left ventricular wall when collaterals were present. More often, the inferior wall showed normal contraction with total occlusion of the right coronary artery and collaterals [52%, p less than 0.001 compared with left anterior descending artery (LAD)]. The prevalence of inferior myocardial infarction was 39%, with collateral circulation to the totally occluded right coronary artery. The respective prevalence of anterior infarction and total occlusion in the left coronary artery was 58% (p less than 0.02). The presence or absence of collaterals had no obvious influence on ST-segment response during bicycle ergometer test. In triple-vessel disease, peak work capacity was better when collaterals to LAD were not jeopardized (427 kpm) than when jeopardized (321 kpm) (p less than 0.02).     

Distribution of the collateral blood flow at the lateral border of the ischemic myocardium after acute coronary occlusion in the pig and the dog

Summary Residual blood flow in pigs (n=8) and dogs (n=11) was measured by tracer microspheres (⁵⁸Sr) 1 hour after occlusion of the left anterior descending coronary artery (LAD). Collateral blood flow was distinguished from overlap flow, defined as the blood flow of non-ischemic myocardium interdigitating into the ischemic area, by direct LAD injection of isotope-labelled microspheres (¹²⁵I) prior to ligation. In the center of the acutely ischemic pig myocardium the residual blood flow, i.e., the myocardial perfusion remaining after LAD occlusion, was 0.01±0.01 ml/min/g subendocardially and 0.02±0.01 ml/min/g subepicardially, as estimated with⁸⁵Sr-labelled microspheres. These values were significantly lower than the corresponding values for the dog, 0.13±0.05 ml/min/kg (p<0.05) subendocardially and 0.28±0.08 ml/min/g (p<0.01) subepicardially. In the lateral aspects of the ischemic area, calculations of overlap flow were made with the aid of the distribution of the microspheres injected into the LAD. Values of the residual blood flow were normalized and nonischemic myocardial perfusion was set to 100 units. In subepicardial layers of the myocardium with calculated overlap flows corresponding to 20, 50 or 80 units, respectively, the residual blood flow (overlap flow + collateral flow) actually measured in the pig was 31±4 55±4 and 75±7 units and in the dog 65±6, 79±5 and 91±2 units. The values for the dog were significantly different from the respective value for the pig (p<0.01). In the subendocardial layers the difference between the two species regarding residual blood flow was similar, although the difference was statistically significant only for myocardium with a calculated overlap flow of 80 units. When the calculated overlap flow was subtracted from the measured residual blood flow, the collateral blood flow was found to be extensive in the dog and virtually absent in the pig.When, in the dog, the collateral blood flow across the lateral border of the ischemic area was related to the amount of myocardium it supplies, it was found to be homogeneously distributed. Thus neither subendocardially nor subepicardially could a gradient of collateral blood flow be detected. It is concluded that in the pig the collateral blood flow is almost nil throughout the acutely ischemic myocardium, both in subendocardial and subepicardial layers. In contrast, the dog has an extensive collateral flow. No lateral gradient of this collateral blood flow could, however, be detected.     

Damage to the collateral circulation by ptca of an occluded coronary artery

In this report, a patient is described with an occluded left circumflex artery, in whom the corresponding myocardium was protected at rest by sufficient collateral circulation. Because of angina pectoris class III, a PTCA of that occluded vessel was performed, complicated by a large dissection. Recruitable collateral flow, assessed from pressure calculations by a new technique, suddenly decreased at the very moment of dissection. This was accompanied by resting pain and ischemia on the ECG. This case report confirms the hypothesis that the collateral circulation can be damaged by PTCA and emphasizes that every PTCA implies a definite risk, even in case of an occluded coronary artery filled by collaterals.     

Influence of the ischemic coronary bed on collateral blood flow

Summary The purpose of this study was to determine the influence of the resistance of the terminal vascular bed of an occluded coronary artery on collateral blood flow and collateral resistance. In 6 anesthetized dogs, left anterior descending coronary artery (LAD) was ligated, cannulated, and the terminal vascular bed was occluded by latex microspheres (diameter: 25). Retrograde flow was measured using a new technique, which allowed control of outflow pressure of retrograde flow (PRF) at the LAD cannula. When retrograde flow was interrupted, pressure in the occluded vessel represented collateral perfusion pressure (CPP) within the border zone of the ischemic vessel. Collateral resistance was determined dividing the pressure difference across the collateral bed (CPP-PRF) by retrograde flow. Variation of PRF was used as a model for changes in resistance of the ischemic bed. Retrograde flow fell when PRF was increased from 11.0±3.0 ml×min^–1×100 g^–1 (PRF=0) to 8.3±2.4 (p<0.01) (PRF=24.6±6 mm Hg). For the same PRF range, collateral resistance fell from 9.68±2.96 to 8.30±2.50 mm Hg×ml^–1×min×100 g (p<0.01). These results indicate that the vascular resistance of the terminal ischemic bed may considerably influence collateral blood flow and resistance.This study was supported in part by DFG grant Er 100/3-1     

Effects of dilevalol in the anesthetized pig with a partially occluded coronary artery

Summary The beta-adrenoceptor antagonist dilevalol in a total dose of 430 g/kg IV, potently suppressed isoprenaline-induced increases in heart rate and max LVdP/dt (dose ratios of 42±6 and 38±5, respectively, in anesthetized pigs), but a dose of 1430 g/kg did not appreciably modify phenylephrine-induced increases in arterial blood pressure (dose ratio< 4) in both anesthetized and conscious pigs. The actions of dilevalol on ischemic myocardium of anesthetized pigs were investigated following a reduction of left anterior descending artery flow by 85–90%. Dilevalol (300 g/kg), administered after 15 minutes of ischemia, did not affect the ischemia-induced changes in systemic hemodynamics (such as heart rate, max LVdP/dt and cardiac output), myocardial perfusion, and wall-thickening of the ischemic segment during the following 15 minutes of ischemia and 2 hours of reperfusion. The reasons for the lack of antiischemic actions are most likely the absence of negative chronotropy and an absence of afterload reduction by dilevalol.     

Coronary collateral circulation behaviour and myocardial viability in chronic total occlusion treated with coronary angioplasty

Aims We explored the role of microcirculation integrity followingthe chronic occlusion of an infarct-related artery to assessthe behaviour of collateral circulation during and after reperfusionby coronary angioplasty Methods and Results Eighteen patients with a proximally occluded left anterior descendingartery and firm evidence of intercoronary collateral circulationwere studied with selective coronary angiography and selectiveintracoronary myocardial contrast echocardiography, before coronaryangioplasty, and at 5 and 15min and 12h later. Myocardial enhancementduring myocardial contrast echocardiography was evaluated witha semiquantitative score (0–3), which was correlated tobasal and 6 months’ regional left ventricular wall motionresults. 16/18 procedures were successfully performed; fourpatients with an inadequate acoustic window were excluded. Restenosiswas evident at the 6 months’ follow-up in two patients.Basal myocardial contrast echocardiography indicated that 81/192segments from the left anterior descending coronary artery and90/192 from the right coronary artery were perfused; no perfusionwas observed in 21 segments either before or after coronaryangioplasty. After coronary angioplasty, the angiographic intercoronarycollateral circulation immediately disappeared, and myocardialcontrast echocardiography revealed that there was a progressivereduction of segments perfused by the right coronary arteryand an increase in segments perfused by the left anterior descendingcoronary artery. Regional left ventricular wall motion analysisdemonstrated that there was abnormal motion in 51/192 segments.There was no improvement in segments with score 0 and abnormalmotion after 6 months (100% sensitivity), but 16/17 segmentswith score 3 did show an improvement (98% specificity). Thepredictive value of intermediate scores (1–2) in detectinglong-term improvement, was only 43%. Conclusion These data show that the adaptive mechanism observed in thebehaviour of epicardial and microvascular circulation afterreperfusion of a chronic occluded infarct-related artery canvary. In addition, this study clearly shows that microvascularintegrity detected by myocardial contrast echocardiography canprovide myocardial viabilityThe European Society of Cardiology     

Coronary collateral circulation: Effects on outcomes of acute anterior myocardial infarction after primary percutaneous coronary intervention

Background To investigate the effects of collateral coronary circulation on the outcome of the patients with anterior myocardial infarction (MI) with left anterior desending artery occlusion abruptly. Methods Data of 189 patients with acute anterior MI who had a primary percutaneous coronary intervention (PCI) in the first 12 h from the onset of symptoms between January 2004 and December 2008 were retrospective analyzed. Left anterior descending arteries (LAD) of all patients were occluded. LADs were reopened with primary PCI. According to the collateral circulation, all patients were classified to two groups: no collateral group (n = 111), patients without angiographic collateral filling of LAD or side branches (collateral index 0) and collateral group (n = 78), and patients with angiographic collateral filling of LAD or side branches (collateral index 1, 2 or 3). At one year’s follow-up, the occurrence of death, reinfarction, stent thrombosis (ST), target vessel revascularization and readmission because of heart failure were observed. Results At one year, the mortality was lower in patients with collateral circulation compared with those without collateral circulation (1% vs. 8%, P = 0.049), whereas there were no differences in the occurrence of reinfarction, ST, target vessel revascularization and readmission because of heart failure. The occurrence of composite of endpoint was lower in patients with collateral circulation compared with those without collateral circulation (12% vs. 26%; P = 0.014). Conclusions Pre-exist collateral circulation may prefigure the satisfactory prognosis to the patients with acute anterior MI after primary PCI in the first 12 h of MI onset.     

Influence of coronary collateral flow on restenosis following primary angioplasty for acute myocardial infarction.

We investigated the influence of collateral flow on restenosis in 156 consecutive acute myocardial infarction (AMI) patients treated with primary angioplasty within 12 hr of symptom onset. Collateral flow was quantitatively assessed using the pressure-derived fractional collateral flow (PDCF) index. Follow-up angiography was performed at 6 months. The patients were classified into two groups according to the PDCF index: group I (PDCF index > 24%; n = 55) with good collaterals and group II (PDCF index < or = 24%; n = 101) with poor collaterals. Baseline characteristics were similar between the two groups, with the exception of peak levels of creatine kinase, angiographic collaterals, and TIMI flow 3 after intervention. The binary restenosis rate was 31.8% in group I and 32.9% in group II (P = NS). Use of the stents was the only independent predictor of binary restenosis. In conclusions, well-developed collaterals measured by PDCF may not predict restenosis following primary angioplasty for AMI.     

Increase in myocardial collateral blood flow during repeated brief episodes of ischemia in the awake dog

Summary The purpose of this study was to determine whether coronary collateral blood flow changes in response to repeated brief periods of ischemia in dogs in which no attempt has been made to stimulate collateral vessel development. The dogs were instrumented with aortic and left atrial catheters and a balloon occluder on the left circumflex coronary artery and were studied in the awake state the following day. Blood flow to the collateral dependent myocardium was measured using 9 radioactive microspheres during four coronary occlusions of two minutes duration, each separated by one hour of reperfusion. A small but statistically significant increase in mean collateral blood flow was noted between the first and fourth occlusions; .03 to .05 ml/min/g. These data suggest that transient periods of brief ischemia may result in increases in collateral blood flow.This study was supported in part by the National Institutes of Health Grant HL 18468 and the Medical Research Service of the Veterans Administration.     

Coronary collateral vessels in patients with previous myocardial infarction

To assess the degree of collateral vessels after myocardial infarction, coronary angiograms, left ventriculograms, and exercise thallium-201 myocardial scintigrams of 36 patients with previous myocardial infarction were reviewed. All 36 patients had total occlusion of infarct-related coronary artery and no more than 70% stenosis in other coronary arteries. In 19 of 36 patients with transient reduction of thallium-201 uptake in the infarcted area during exercise (Group A), good collaterals were observed in 10 patients, intermediate collaterals in 7 patients, and poor collaterals in 2 patients. In 17 of 36 patients without transient reduction of thallium-201 uptake in the infarcted area during exercise (Group B), good collaterals were seen in 2 patients, intermediate collaterals in 7 patients, and poor collaterals in 8 patients (p less than 0.025). Left ventricular contractions in the infarcted area were normal or hypokinetic in 10 patients and akinetic or dyskinetic in 9 patients in Group A. In Group B, 1 patient had hypokinetic contraction and 16 patients had akinetic or dyskinetic contraction (p less than 0.005). Thus, patients with transient reduction of thallium-201 uptake in the infarcted area during exercise had well developed collaterals and preserved left ventricular contraction, compared to those in patients without transient reduction of thallium-201 uptake in the infarcted area during exercise. These results suggest that the presence of viable myocardium in the infarcted area might be related to the degree of collateral vessels.     

关于冠脉侧支循环影响因素的研究进展

冠脉侧支循环(coronary collateral circulation,CCC)是指同一或不同冠脉血管之间相互吻合的微小血管。这些微小血管在冠状动脉狭窄的情况下有重塑和扩张的潜能,为受损心肌提供了另一种血液供应来源。侧支循环对冠心病患者有保护作用,即减小心肌坏死面积,保护心脏功能,减少心室扩张,减少室壁瘤的发生等。临床上发现,冠心病人群中侧支生成开放与否存在很大差异。目前对于引起不同个体之间侧支生成差异的影响因素存在争议。本文就冠状动脉侧支生成的机制,各因素与侧支生成的相关性进行综述。     

Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol.

BACKGROUND: The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS: Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS: Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.     

Effects of nifedipine on collateral blood flow at the lateral border of the acutely ischemic myocardium

Summary In open-chest dogs (n=5) the effects of nifedipine (25 g/kg infused over a period of 15 min) on the collateral blood flow after left anterior descending coronary artery (LAD) ligation were separated from those on heterogeneous blood supply, i.e. flow of collateral origin plus flow in nonischemic myocardium projecting into the ischemic area. This separation was possible using a technique based on microspheres, allowing analysis of perfusion via the left anterior descending coronary artery (LAD). Secondary effects on the ischemic heart induced by the hypotensive effect of nifedipine per se were minimized by counterbalancing the blood pressure change with an intra-aortic balloon. Nifedipine increased non-ischemic myocardial blood flow in the subendocardium from 1.11±0.10 to 2.71±0.17 (p<0.001) and in the subepicardium from 1.12±0.08 to 3.95±0.49 (p<0.001) (ml/min/g, mean ±SE). Collateral blood flow in the centre of the ischemic area was not affected by nifedipine. In the subendocardium, it was 0.12±0.05 before and 0.09±0.09 after nifedipine, and in the subepicardium, the corresponding values were 0.21±0.10 and 0.29±0.04, respectively. At the lateral ischemic border, the nifedipine-induced increase in myocardial blood flow was only directed to the admixed normal tissue. When the blood flow was corrected for this overlapping non-ischemic tissue, no significant effect of nifedipine was measurable in the subendocardial blood flow, which was 0.12±0.03 before and 0.18±0.04 ml/min/g after drug administration. However, in the subepicardium, the collateral blood flow was significantly reduced from 0.33±0.09 to 0.15±0.05 (p<0.05). It is concluded that nifedipine was able to decrease collateral blood flow at the lateral border, while leaving the blood flow unaffected in the centre of the ischemic are.     

冠心病患者冠状动脉侧支循环形成的相关因素

目的:探讨冠状动脉侧支循环形成的意义及影响侧支循环形成的相关因素。方法:冠状动脉造影中发现有侧支循环形成者47例作为研究组,以病变程度相同但无侧支循环形成者58例作为对照组;同时超声心动图检查病变局部室壁运动情况。结果:侧支循环形成与糖尿病、吸烟呈负相关,与服用他汀类药物呈正相关,而与性别、年龄、胸痛时间、有无高血压病、有无高脂血症、家族史、冠状动脉病变支数、服用ACEI类、硝酸酯类药物无关。结论:侧支循环多出现在病变严重的冠心病患者,糖尿病、吸烟是侧支循环形成的不利因素,服用他汀类药物能促进侧支循环形成;糖尿病患者即使形成侧支循环,对心功能的保护作用也较差。     

The J-curve relationship between diastolic pressure and coronary collateral circulation in patients with single chronic total occlusion

Background

In our previous study, we had shown that high diastolic blood pressure (DBP) was positively related to well-developed coronary collateral circulation (CCC). This study sought to find out the more precise relationship between DBP and CCC.

Methods and results

To investigate this, we conducted a study of 671 patients with single chronic total occlusion of coronary artery. The DBP of the patients was divided into six groups: ≤65 mmHg, >65–≤75 mmHg, >75–≤85 mmHg, >85–≤95 mmHg, >95–≤105 mmHg, >105 mmHg). The extent of CCC was graded as poorly-developed or well-developed collaterals according to Rentrop classification. There was a J-curve relationship between the level of DBP and the incidence of poorly-developed collaterals.

Conclusion

The relationship between DBP and CCC is similar to the J-curve relationship between DBP and cardiovascular risk. The influence of DBP on the development of CCC may be one of the pathophysiologic mechanisms of the J-curve phenomenon relating DBP to cardiovascular risk.     

Flow support catheter for prolonged maintenance of coronary blood flow

A newly designed flow support catheter with a supporting wire mesh cage which can be expanded into a tubular configuration and then readily reduced was evaluated in mongrel dogs. Regional myocardial blood flow (RMBF) was measured using the radioactive microsphere technique in the area of both balloon-denuded instrumented and control non-instrumented coronary arteries following placement of either a fixed-wire or a higher profile rapid exchange flow support catheter. At 5, 20, and 180 min following delivery and expansion of either device, RMBF was not significantly different in left ventricular subepicardium and subendocardium perfused by the instrumented vs. the control coronary arteries. Angiography demonstrated widely patent instrumented arteries in 15/18 dogs; in no dog was side branch occlusion observed. Significant cage thrombus deposition was seen angiographically in 3 animals causing temporary total coronary occlusion in 1. Following reduction and removal of the flow support catheter, vessel patency was present in all dogs. The flow support catheter is an effective endovascular stenting device capable of providing structural arterial support, while simultaneously maintaining distal coronary blood flow. It is envisioned that the primary application of this catheter will be to enable primary salvage of vessels acutely injured during coronary angioplasty, by “tacking up” intimal flaps for an extended period. It may also provide a bridge to emergency surgical revascularization.     

慢性完全闭塞病变侧支循环与心功能恢复的关系

目的应用实时三维超声心动图(RT3DE),评价既往有心肌梗死病史的冠状动脉慢性完全闭塞病变(CTO)患者血运重建前后整体和局部心功能变化。方法选择38例既往有心肌梗死病史并血运重建成功的CTO患者,将其分为两组:A组为术前显示CTO处存在通畅的侧支或逆灌血流患者22例;B组为术前显示CTO处无侧支或逆灌血流患者16例。所有患者术前、术后6周均行RT3DE及二维超声心动图检查和室壁运动评价。结果A组患者术后6周LVEF由(53.8±5.6)%增加至(62.9±6.3)%,差异有统计学意义(P<0.05),左心室局部室壁运动显著改善(P<0.05),B组患者术后6周LVEF由(49.7±5.0)%增加至(51.0±4.8)%,差异无统计学意义。左心室局部室壁运动改善不明显。结论使用RT3DE评价既往有心肌梗死病史的CTO患者心脏功能和血运重建对于CTO存在良好侧支循环并保持通畅的患者,左心室整体和局部心功能明显提高。     

Coronary collaterals: Role in restoration of blood flow and preservation of cardiac function during exercise

Summary Chronically instrumented dogs were studied at rest and during exercise on two occasions 10–12 weeks apart. The left circumflex coronary artery (LCf) was initially constricted in all dogs. By the time of the second study the LCf was still patent in 9 dogs and had become occluded in 6. In the dogs with chronic coronary occlusion, collaterals restored myocardial flow to normal both at rest and during exercise, and there were no adverse hemodynamic effects when running. Conversely, in dogs with constricted but patent LCfs collateral development was inadequate to return ischemic flows to normal following transient coronary occlusion, and occlusion during exercise produced significant myocardial failure. Thus coronary collaterals can compensate for decreased antegrade coronary flow.This study was supported by National Heart, Lung and Blood Institute Grant HL-17809.     

Atrial natriuretic peptide augments coronary collateral blood flow: A study during coronary angioplasty

Background and hypothesis: In vitro studies have shown that atrial natriuretic peptide (ANP) causes relaxation of pre-constricted blood vessel strips and inhibits the contraction of isolated vessels in response to norepinephrine and angiotensin II. The present study examined the effects of exogenous ANP on the coronary collateral blood flow during angioplasty. Methods: We studied 15 patients undergoing elective balloon angioplasty during the second and third balloon inflations. A Doppler flow guidewire was advanced distal to the lesion and used for the estimation of coronary blood flow velocity. After the second balloon inflation, 25 ng/kg/min of ANP were administered intracoronarily for 8 min. Electrocardiogram, pressure, and flow velocity were recorded immediately before each balloon deflation. Fourteen other patients served as controls and received normal saline infusion. Results: Velocity time integral increased from 65 ± 40 to 79 ± 46 mm (p < 0.05) during the third balloon inflation, whereas ST deviation decreased from 1.3 ± 0.9 to 0.7 ± 1.0 mV (p< 0.05). These variables did not change in the control group during the two tested balloon inflations. Conclusion: Exogenous ANP augments coronary collateral blood flow and ameliorates myocardial ischemia during angioplasty.