Part I: Microvascular injury In patients with an acute myocardial infarction (AMI), up to 40% of patients show persisting microvascular injury (MVI). In order to investigate MVI and the hemodynamic consequences of an successfully revascularized AMI, we performed post-PCI intracoronary measurements both in AMI patients and in a swine AMI-model. As a control, similar measurements were taken in patients without obstructive CAD and in swine prior to induced AMI. Measurements between patients and swine were almost identical. Post-PCI arteries showed a significant decrease in hyperemic flow and an increased baseline flow. This constitutes a decrease of the coronary flow reserve (CFR), despite the successful revascularization. Decrease in post-infarction CFR was significantly associated with an increase in intramyocardial hemorrhage, which is known to be a direct consequence of MVI. Given the fact that CFR in patients without CAD was similar to the healthy porcine model, where coronary microvascular dysfunction is certainly absent, it can be concluded that the reduction of post-AMI CFR –and thereby MVI– occurs independently of pre-existing microvascular dysfunction. These findings affirm that MVI and its hemodynamic consequences are solely and directly the effect of acute ischemia-reperfusion. Interestingly, successful PCI does not halt the progression of MVI, which typically reaches its maximum hours after revascularization. For a long time it was unclear whether MVI was merely a consequence of ischemia-induced damage, or that reperfusion itself has a harmful effect. We aimed to distinguish the effects of ischemia and reperfusion on the coronary microcirculation in an experimental rat model. We show that compared to ischemia alone, the addition of in-vivo reperfusion inflicts major additional damage on endothelial cells and significantly increases vascular permeability and extravasation of erythrocytes, which is also seen in AMI patients. Of importance is that the aforementioned endothelial damage was not seen in the groups that were exposed to ischemia alone.   Part II: Collateral Circulation Stimulation of collateral artery growth (i.e. arteriogenesis) is a promising alternative therapy for patients with severe CAD, who are not suitable for or do not have access to mechanical revascularization. Ideally, patients with poor collateral response are selected prior to severe CAD. We postulated that one’s ability to develop an adequate collateral network is not organ specific. We investigated the collateral circulation in the hand and show that after complete occlusion of the radial artery, digital perfusion is ensured via innate collateral connections originating from the ulnar artery. Using Laser-Doppler Perfusion Imaging (LDPI) the palmar collateral flow index (Palmar CFI) was calculated, which shows to what degree the collateral circulation restores perfusion in presence of an complete arterial occlusion. We also show that besides LDPI, a Palmar CFI could be reliably calculated using non-invasive digital blood pressure measurements. Data shows that the Palmar CFI significantly correlates with de coronary CFI, in patients with a chronic total occlusion (CTO), which implies collateral coherence between vascular beds. Interestingly, data shows that patients with a poor native collateral network, i.e. a low palmar CFI, fail to develop high-performance coronary collaterals in presence of a CTO. However, a high palmar CFI does not always coincide with a high coronary CFI. This suggests other factors influence the development of coronary collaterals as well. Using a murine hind-limb model, we show that inhibition of galectin-2 by a single-domain antibody significantly increases collateral artery growth. Furthermore, we demonstrate that this arteriogenic response is caused by the skewing of macrophage subsets. After inhibition of galectin-2, perivascular macrophages showed a higher fraction of the M2-phenotype, which are known to resolve inflammation, and help tissue healing. Furthermore, inhibition of galectin-2 did not increase atherosclerosis plaque burden, in contrast to prior pro-arteriogenic targets.