Conceptualizing conduction as a pliant vasomotor response: impact of Ca2+ fluxes and Ca2+ sensitization

Conducted vasomotor responses depend on electrical spread in the vascular wall and its translation into vasomotor responses. Our computational investigation highlights how the regulatory state of the contractile apparatus can shape conduction without interfering with the underlying electrical spread. Contractile machinery is regulated, e.g., by regional endocrine or mechanical signals. We further illustrate how regional contractile regulation can work cooperatively with electrical spread to optimize perfusion to local tissue demands.

Conceptualizing conduction as a pliant electrical response: impact of gap junctions and ion channels

Conducted vasomotor responses depend on initiation and spread of electrical phenomena along arterial walls and their translation into contractile responses. Using computational approaches, we show how subtle but widespread regulation of gap junctions and ion channels can modulate the range and amplitude of electrical spread. Ion channels are regulated by endocrine and mechanical signals and may differ regionally in networks. Subregional electrical changes are not spatially confined but may affect electrical conduction in neighboring regions.

Differential vasomotor responses to isocapnic hyperoxia: cerebral versus peripheral circulation

Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.

P2706Persistent impairment of coronary endothelial vasomotor responses is related to atheroma plaque progression in the infarct-related coronary artery of AMI survivors

Background Although coronary endothelial vasomotor dysfunction predicts future coronary events, there are few human studies showing the relationship between endothelial vasomotor dysfunction and atheroma plaque progression in the same coronary artery. Purpose This study examined whether endothelial vasomotor dysfunction is related with atheroma plaque progression in the infarct-related coronary artery of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessment of coronary plaque size with intravascular ultrasound (IVUS) and coronary vasomotor responses to acetylcholine (ACh). Methods This study included 50 patients with a first acute STEMI due to occlusion of left anterior descending coronary artery (LAD) and successful reperfusion therapy with percutaneous coronary intervention (PCI). IVUS and vasomotor response to ACh in the LAD were measured within 2 weeks after AMI (1st test) and repeated 6 months (2nd test) after AMI under optimal anti-atherosclerotic therapies. The impairment of vasomotor response to ACh was defined as <10% of the responses to ACh in 25 control subjects. Results Percent atheroma volume (PAV) and total atheroma volume (TAV) in the LAD progressed over 6 months of follow-up in 18 and 14 patients, respectively. Epicardial coronary artery dilation and coronary blood flow increase in response to ACh were persistently impaired at both the 1st and 2nd tests in 18 and 19 patients. In logistic regression analysis, the progression of PAV and TAV was significantly associated with patients with the persistent impairment of epicardial coronary diameter and blood flow response to ACh (PAV, OR, 6.2 [95% CI, 1.4–28], P=0.02 and 4.3 [1.2–16], P=0.03, respectively. TAV, 6.0 [1.4–26], P=0.02 and 5.5 [1.4–21], P=0.01, respectively). The progression of PAV and TAV had no significant association with the coronary vasomotor responses to ACh at the 1st test, traditional risk factors, PCI-related variables, medications, and the coronary vasomotor responses to sodium nitroprusside, an endothelium-independent vasodilator. Conclusions Persistent impairment of endothelial vasomotor function in the conduit arterial segment and the resistance arteriole was related to atheromatous plaque progression in the infarct-related coronary arteries of STEMI survivors despite optimized anti-atherosclerotic therapies. Acknowledgement/Funding None

Functional recovery of the microcirculation during skeletal muscle regeneration

Skeletal muscle has a remarkable capacity to regenerate following injury, and although muscle regeneration has been studied extensively, little is known about the recovery of the skeletal muscle microcirculation during regeneration. To determine the restoration of blood flow regulation during skeletal muscle regeneration, this dissertation explored the recovery of vasomotor responses to physiological agonists and of functional vasodilation in response to muscle contraction. A novel injury model in the mouse gluteus maximus muscle was developed to study the microcirculation in vivo using intravital microscopy at welldefined time points (5, 10, 21 and 35 days) post injury compared to uninjured Control muscles. Studies encompassed feed arteries and the principal branches (1st, 2nd and 3rd order) of arteriolar networks comprising the resistance vasculature. Vasomotor responses to agonists and active force developed by muscle fibers recovered by 21d, however functional vasodilation required [about]35d to recover. This research provides novel insight into when and to what extent blood flow regulation is restored during skeletal muscle regeneration and provides novel perspective towards developing therapeutic strategies for restoring skeletal muscle function during recovery from injury.