Innate Human Collateral Supply to Different Vascular Regions
Both clinical and experimental studies demonstrate the importance of the pre-existing, ie innate collateral supply in different vascular regions. Furthermore, pathophysiological considerations and experimental data imply an important role for the association of collateral function between different vascular regions.
STUDY HYPOTHESES 1. In the absence of atherosclerotic stenoses, there is a direct association between the collateral function in the coronary, renal and peripheral circulation. 2. The increase in plasma renin in response to a unilateral main renal artery balloon occlusion is inversely related to its functional collateral supply. 3. The decrease in renal vein oxygen saturation in response to a unilateral main renal artery occlusion is inversely related to its functional collateral supply.
研究概览
详细说明
Background
PROTECTIVE EFFECT AND INTER-INDIVIDUAL DISTRIBUTION OF THE COLLATERAL CIRCULATION IN DIFFERENT VASCULAR REGIONS
Of all vascular regions, the collateral circulation of the heart is probably the most extensively studied since the initial studies by Fulton.1 The clinical importance of the coronary collateral circulation2 has been established by numerous investigations demonstrating a protective role of well vs. poorly grown coronary collateral arteries.
Whereas involvement of the peripheral arterial network by obstructive arterial disease is frequently asymptomatic, it is, nevertheless, relevant through the association with increased mortality and as a strong predictor of adverse cardiovascular outcomes. The clinical relevance of the collateral circulation in the lower extremities can be epitomized by the discrepancy of frequently encountered long segmental occlusions and the rare occurrence of severe ischemia or amputation. With regard to a systematic evaluation of this apparently well-collateralized region, it was, however, only very recently that assessment using a direct and quantitative method was performed.
Regarding the kidney, the collateral circulation has hitherto been subject to systematic research only in experimental studies,while data in humans are sparse and limited to angiographic assessment. While the hypertensive effect of renal arterial constriction is well-known since the seminal studies of Goldblatt in 1934, the effect of renal collaterals in this context has been neglected despite the readily apparent effects therefrom in the same experiment. The duration of the ensuing hypertension was only short in Goldblatt's experiments with dogs, an observation explained by the abating effect of efficient collaterals on renal artery constriction and consequently developing reduction of the renal ischemia. In humans, only limited and indirect data on the compensatory effect of the renal collateral circulation in the setting of renal arterial constriction exist.The ratio of selective renin concentrations sampled from the renal vein of both kidneys (affected/unaffected) is commonly used to assess the hemodynamic significance of a unilateral renal artery stenosis. Ernst et al., in 37 patients with unilateral renal stenosis, determined the (selective) renal vein renin ratio and additionally performed angiography for presence of renal collaterals( documented in 68%). Renal collaterals tended to normalize renin excretion in a kidney affected by renal artery stenosis. Indeed, 7 patients with a severe stenosis and visible renal collaterals had a normal renin ratio below the cut-off of 1.4. The clinical relevance of renal artery stenosis is underscored by its prevalence in a significant proportion of patients undergoing routine cardiac angiography.22, 23 In the above context, it is noteworthy that hypertension is not present in almost one half of patients with angiographically significant narrowing of a renal artery.
PRE-EXISTING COLLATERAL CIRCULATION AND ITS INTRA-INDIVIDUAL DISTRIBUTION As alluded to before, acute vascular occlusion in arteriosclerosis can ensue in the absence of relevant narrowing. In this situation, solely the native, pre-existing collateral extent can lessen the ischemic tissue injury. On the other hand, the gradual narrowing of a vessel allows development of large arterial anastomoses from pre-existing smaller arterioles in the process known as arteriogenesis. The notion that the pre-existing collateral extent nevertheless remains the basis for the capacity of anastomoses to enlarge is supported by an instructive experimental study by Zbinden et al.: Flow recovery after superficial femoral artery ligation correlated strikingly with the pre-existing collateral extent. Thus, mice with an already high level of pre-existing collaterals had concordantly high flow recovery, while mice with low levels of pre-existing collaterals had low flow recovery.
Given the systemic process of atherosclerosis, the preformed or innate human collateral function in the different vascular regions mentioned before is of interest. On a patient level, this relates to the intra-, as opposed to the inter-individual distribution of the collateral network. While the inter-individual distribution of collateral function in humans has been shown to vary widely also in the absence of vascular narrowings, recent experimental studies in mice have shown that innate collateral extent is shared qualitatively in different tissues. However, in humans, the association between the collateral function in different vascular regions in humans has so far not been investigated.
In conclusion, both clinical and experimental studies demonstrate the importance of the pre-existing, ie innate collateral supply in different vascular regions. Furthermore, pathophysiological considerations and experimental data imply an important role for the association of collateral function between different vascular regions.
Objective
To determine the in vivo prevalence and distribution of functional collateral supply in the coronary, renal and peripheral circulation, and the intra-individual association of collateral function between the different vascular territories. Additionally, the effect of renal collaterals on the response of the kidney to a short bout of ischemia will be investigated.
Methods
DESIGN Prospective, comparative observational study with collateral function measurements in the coronary, renal and superficial femoral artery.
PRIMARY STUDY ENDPOINT Pressure-derived collateral flow index (CFI) SECONDARY STUDY ENDPOINTS Intracoronary ECG ST segment shift during temporary coronary balloon occlusion; plasma renin concentration before, immediately and 10 minutes after main renal artery occlusion, sampled from the suprarenal inferior vena cava ; transcutaneous oxygen tension (tcpO2) as obtained during left superficial femoral artery occlusion from the left anteromedial lower leg.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Bern、瑞士、3010
- Department of Cardiology, Bern University Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Age > 17 years
- Referred for elective coronary angiography
- Written informed consent to participate in the study
Exclusion Criteria
- Acute coronary syndrome
- Severe cardiac valve disease
- Congestive heart failure NYHA III-IV
- History of renal disease with normal renal function/ solitary kidney
- Renal (abnormal serum creatinin level) or hepatic failure
- Peripheral artery disease > stage I
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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Coronary artery disease
With coronary artery disease
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No coronary artery disease
Without coronary artery disease
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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Collateral Flow index
大体时间:At baseline
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At baseline
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次要结果测量
结果测量 |
大体时间 |
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Intracoronary ST segment elevation
大体时间:At baseline
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At baseline
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Transcutaneous oxygen tension (tcpO2)
大体时间:At baseline
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At baseline
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Plasma renin concentration
大体时间:Before, immediately after and 10 minutes after main renal artery occlusion
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Before, immediately after and 10 minutes after main renal artery occlusion
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Renal vein oxygen saturation
大体时间:Before, during and immediately after main renal artery occlusion
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Before, during and immediately after main renal artery occlusion
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合作者和调查者
调查人员
- 首席研究员:Christian Seiler, MD Prof、Department of Cardiology, Bern University Hospital, Switzerland
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他研究编号
- 185/13
- 2451 (其他标识符:University Hospital Berne)
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