The Development of Collateral Circulation in the Pig and Dog Heart

Schäper, Wolfgang; Jageneau, A; Xhonneux, R.

doi:10.1159/000165875

Cited by 118 publications

(44 citation statements)

References 3 publications

(6 reference statements)

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“…In addition, most studies have focused on evaluation of the therapeutic efficacy of vascular endothelial growth factor (VEGF) A, which primarily targets the endothelial cell compartment (5,12,17,21,22). Unlike rodents and dogs, pigs usually lack sufficient native collaterals to prevent major infarction after coronary artery occlusion (23)(24)(25). Thus, the pig myocardial infarction model is the most relevant and ideal animal system to human coronary artery disease.…”

mentioning

confidence: 99%

Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs

Lu¹,

Xu²,

Zhang³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Establishment of functional and stable collaterals in the ischemic myocardium is crucial to restoring cardiac function after myocardial infarction. Here, we show that only dual delivery of a combination of angiogenic and arteriogenic factors to the ischemic myocardium could significantly reestablish stable collateral networks and improve myocardial perfusion and function. A combination of FGF-2 with PDGF-BB, two factors primarily targeting endothelial cells and vascular smooth muscle cells, remarkably promotes myocardial collateral growth and stabilizes the newly formed collateral networks, which significantly restore myocardial perfusion and function. Using various members of the PDGF family together with FGF-2 in an angiogenesis assay, we demonstrate that PDGFR-␣ is mainly involved in angiogenic synergism, whereas PDGFR-␤ mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease.angiogenesis ͉ growth factor ͉ ischemia ͉ myocardial infarction ͉ neovascularization A therosclerosis-induced coronary artery disease is the leading cause of morbidity and mortality in Western societies and increases at an alarming rate in developing countries (1). Usually, progressive atherosclerosis results in plaque rupture and thrombosis of major coronary arteries, leading to angina, myocardial infarction, and heart failure (2). Except for surgical interventions, an effective therapeutic method for treatment has been lacking. Although delivery of proangiogenic factors to the ischemic myocardium to stimulate collaterogenesis and to improve myocardial perfusion and function is a straightforward idea proposed for Ͼ30 years, clinical evaluation of these individual proangiogenic molecules has produced unfulfilled promises (3-5). After more than a decade of clinical practice with different single proangiogenic factors for the treatment of ischemic disorders, almost all large randomized, double-blinded, and placebo-controlled human trials have proven to be nonbeneficial (6-8).The clinical failures with this attractive approach have raised several unresolved fundamental issues regarding the basic mechanisms of cardiovascular biology. These include the underlying mechanisms of angiogenesis versus arteriogenesis, choice of proangiogenic agents, monotherapy versus combinatorial therapy, appropriate animal models for preclinical evaluation, optimal drug release systems, and time line of delivery. For improvement of perfusion of high-oxygenated blood in ischemic tissues, it is essential to reestablish functional arterial vascular networks, which should remain stable long-term. Most previous preclinical and clinical studies on the development of proangiogenic therapies for treating ischemic myocardium have been based on monotherapeutic approaches (9-20). These approaches usually lack rationales for understanding the molecular mechanisms of arteriogenesis, for defining molecular targets of the deliverable proangiogeni...

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mentioning

confidence: 99%

Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs

Lu¹,

Xu²,

Zhang³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Figure 4 illustrates the mean nary occlu- . 20'T1 activity in each of 24 radials for the six experimental animals 10 to 14 min after injection. Mean radial profiles from before (control) and 3 days and 6 weeks after LCf ligation are shown.…”

Section: Resultsmentioning

confidence: 99%

Exercise thallium-201 scintigraphy in dogs: effects of long-term coronary occlusion and collateral development on early and late scintigraphic images.

Cohen¹,

Steingart²

1985

Circulation

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To examine the effects of coronary collateral development on thallium-201 (201T1) distribution the left circumflex coronary artery was ligated in eight dogs. Three days later these animals ran on a treadmill, and 201-thallous chloride was injected into the right atrium at peak exercise. Scintigraphic scanning was begun within 10 min and continued for 3 hr. Scanning was repeated weekly for 6 weeks. In the last week radioactive microspheres were injected into the left atrium at peak exercise to measure regional myocardial blood flow. The scintigraphically determined disparity between perfusion of the ischemic and normal myocardium was most marked at 3 days after ligation. This difference gradually lessened over the first 4 weeks until there was no difference in 2017T1 distribution to normally perfused myocardium and tissue distal to the ligation. Concomitant with the improvement in the scintigrams, exercise hemodynamics also improved over this 4 week period with significant increases in cardiac output and decreases in left atrial pressure. Serial coronary angiographic studies in two animals demonstrated the appearance of collaterals in the initial weeks after coronary occlusion, and by 4 weeks the left circumflex artery distal to the obstruction was completely opacified by collateral flow. The ratio of directly measured exercise blood flow to the left circumflex and normally perfused tissues was 0.89 0.08 at 6 weeks after ligation. Scintigraphic 20'Tl redistribution after 3 hr also changed over the weeks after ligation. Three days after ligation washout from the ischemic area was significantly slower than that from the normal myocardium.

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“…Garamella et al4) reported that the development of the intercoronary arteriography paralleled the rise of peripheral coronary pressures in the occluded coronary artery. Schaper et al 5) also described that the peripheral coronary pressure is an indication for the enlargement of intercoronary anastomoses.…”

Section: Discussionmentioning

confidence: 97%

Peripheral Right Coronary Artery Pressure Distal to the Ligation

Yokoyama¹,

Nogi²,

Yokoyama

1972

Jpn Heart J

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SUMMARYThe ligature of right coronary artery near its origin produced low distal right coronary artery pressure, which showed gradual increase day by day, reaching maximum level (70% of the aortic pressure) in 8 postoperative days.The trial to produce rapid increase of the distal right coronary pressure by augmenting the left circumflex coronary pressure by means of roller pump was carried out in normal dogs. But the increase of the distal right coronary artery pressure was only several millimeters mercury. The pressure augmentation of 2 hours in the left side, therefore, could not produce sufficient collaterals from left to right.

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The Development of Collateral Circulation in the Pig and Dog Heart

Cited by 118 publications

References 3 publications

Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs

Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs

Exercise thallium-201 scintigraphy in dogs: effects of long-term coronary occlusion and collateral development on early and late scintigraphic images.

Peripheral Right Coronary Artery Pressure Distal to the Ligation

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