scholarly journals High-altitude rodents have abundant collaterals that protect against tissue injury after cerebral, coronary and peripheral artery occlusion

2020 ◽  
pp. 0271678X2094260
Author(s):  
James E Faber ◽  
Jay F Storz ◽  
Zachary A Cheviron ◽  
Hua Zhang

Collateral number/density varies widely in brain and other tissues among strains of Mus musculus mice due to differences in genetic background. Recent studies have shown that prolonged exposure to reduced atmospheric oxygen induces additional collaterals to form, suggesting that natural selection may favor increased collaterals in populations native to high-altitude. High-altitude guinea pigs ( Cavia) and deer mice ( Peromyscus) were compared with lowland species of Peromyscus, Mus and Rattus (9 species/strains examined). Collateral density, diameter and other morphometrics were measured in brain where, importantly, collateral abundance reflects that in other tissues of the same individual. Guinea pigs and high-altitude deer mice had a greater density of pial collaterals than lowlanders. Consistent with this, guinea pigs and highlander mice evidenced complete and 80% protection against stroke, respectively. They also sustained significantly less ischemia in heart and lower extremities after arterial occlusion. Vessels of the circle of Willis, including the communicating collateral arteries, also exhibited unique features in the highland species. Our findings support the hypothesis that species native to high-altitude have undergone genetic selection for abundant collaterals, suggesting that besides providing protection in obstructive disease, collaterals serve a physiological function to optimize oxygen delivery to meet oxygen demand when oxygen is limiting.

2015 ◽  
Vol 21 (2) ◽  
pp. 175-177 ◽  
Author(s):  
Bulent Kaya ◽  
Fatih Erdi ◽  
Fatih Keskin ◽  
Erdal Kalkan ◽  
Osman Koç

Spontaneous “non-moyamoya” arterial occlusion of the intracranial arteries is very unusual. Progressive occlusion of a major intracranial artery, independently from the etiology, can lead to the development of collateral arterial networks that supply blood flow to distal territories beyond the occlusion. These collateral arteries are typically small and conduct low flows, but the hemodynamic stress within them can lead to aneurysm formation within the collateral network. In this report we present a case of spontaneous internal carotid artery occlusion and collateral network aneurysm for the first time in the literature and discuss the main features of the etiology and endovascular treatment of this rare, challenging aneurysm.


1994 ◽  
Vol 267 (6) ◽  
pp. H2523-H2530 ◽  
Author(s):  
J. L. Unthank ◽  
J. C. Nixon ◽  
M. C. Dalsing

The hemodynamic significance of endothelium-derived relaxing factor (EDRF)-mediated mechanisms in vascular responses to abrupt rat femoral artery occlusion was investigated. Temporary arterial occlusion was produced before and after inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA). Iliac artery blood flow and arterial pressures proximal and distal to the occlusion were measured. Normal vascular compensation included a return of resistance to preocclusion levels and a rise in distal pressure to a plateau within 5 min postocclusion. After treatment with L-NAME and L-NMMA, postocclusion resistance remained elevated by 53 and 36%, respectively. Collateral dilation after occlusion, as indicated by the rise in distal pressure, was prevented by L-NAME but not L-NMMA. Increases in adrenergic tone and mean arterial pressure by phenylephrine did not prevent compensation, suggesting the effects of L-NAME and L-NMMA did not result from elevated sympathetic activation or pressure. The results are consistent with the hypothesis that the stimulated release of endothelium-derived relaxing factor mediates the acute vascular compensation to abrupt arterial occlusion.


Evolution ◽  
2013 ◽  
Vol 68 (1) ◽  
pp. 48-62 ◽  
Author(s):  
Zachary A. Cheviron ◽  
Alex D. Connaty ◽  
Grant B. McClelland ◽  
Jay F. Storz

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Lin Yang ◽  
Xiao Ming Zhang ◽  
Yong Jun Ren ◽  
Nan Dong Miao ◽  
Xiao Hua Huang ◽  
...  

Purpose. To investigate the extrahepatic collateral arteries related to hepatic artery occlusion (HAO) and to determine its benefits in the transarterial management of liver tumors.Methods and Findings. Eleven patients (7 hepatocellular carcinomas, 3 liver metastases, and 1 with hemangioma) with HAO confirmed with digital subtraction angiography (DSA) were admitted to our hospital. Of the 11 patients, 7 were men and 4 were women, with an average age of 41.5 ± 15.5 years (range: 29 to 70 years). DSA was performed to evaluate the collateral routes to the liver. In the 11 patients with HAO, DSA showed complete occlusion of the common hepatic artery in 9 patients and the proper hepatic artery (PHA) in 2 patients. Extrahepatic collateral arteries supplying the liver were readily evident. The collateral arteries originated from the superior mesenteric artery (SMA) in 8 patients, from the gastroduodenal artery in 2 patients, and from the left gastric artery (LGA) in 1 patient. Transcatheter treatment was successfully performed via the collateral artery in all patients except the one who had hemangioma.Conclusions. DSA is an effective method for detecting collateral circulation related to HAO and may provide information to guide transcatheter management decisions.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Huaiping Zhu

Efficient arteriogenesis is vital for recovery after cardiovascular events (such as chronic coronary occlusion, myocardial infarction). Identifying the biological factors that affect arteriogenesis will help design new treatments for patients with chronic arterial stenosis and occlusions. Circulating monocytes and macrophages recruited within the surrounding tissue of collateral vessels following arterial occlusion have been reported to be essential to arteriogenesis in collateral arteries/arterioles because they promote the proliferation of vascular smooth muscle cells (VSMCs) and endothelial cells through secreted cytokines. Although a growing number of putative arteriogenic factors have been identified, the exact mechanisms that regulate collateral remodeling have remained largely unknown. Here we report that AMPK, an energy and redox sensor, is required for monocyte-mediated collateral remodeling. Collateral arteriogenesis was monitored in WT, global AMPKα1 knockout (KO), or macrophage-specific AMPKα1 KO mice with or without hind limb ligation. Compared to WT mice with ligation, global AMPKα1 KO mice displayed significant reduction in blood flow recovery and impaired remodeling of collateral arterioles. Similar impairments were observed in macrophage-specific AMPK α1 KO mice following hind limb ligation. Mechanistically, we found that AMPKα1 promotes the production of growth factors, such as transforming growth factor beta, by directly phosphorylating the inhibitor of nuclear factor kappa B (NF-κB) kinase alpha, resulting in an NF-κB-dependent production of growth factors. Collectively, our findings suggest a novel role for macrophage AMPKα1 in arteriogenesis and collateral remodeling and indicate that AMPKα1 activation might be a therapeutic target for treating occlusive vascular disorders.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Junya Aoki ◽  
Kazumi Kimura ◽  
Norifumi Metoki ◽  
Yohei Tateishi ◽  
Kenichi Todo ◽  
...  

Introduction&Hypothesis: The aim of the present study was to investigate whether administration of edaravone, a free radical scavenger, before or during t-PA administration can increase the rate of early recanalization and improve the clinical outcome in stroke patients with major arterial occlusion. Methods: YAMATO study is an investigator initiated, multicenter (17 hospitals in Japan), prospective, randomized, open labeled study. Acute stroke patients with horizontal (M1) or vertical (M2) portion of the middle cerebral artery occlusion within 4.5 h of onset were studied. The subjects were randomly allocated to the early edaravone (early-E) group (intravenous edaravone [30 mg] was started before or during t-PA administration) and the late edaravone (late-E) group (edaravone was started after t-PA administration). Primary outcome, defined as any early recanalization 1h after t-PA therapy. Secondary outcomes included the rate of the significant recanalization, defined as ≥50% of the territory of the occluded artery on magnetic resonance angiography, or the thrombolysis in cerebral infarction score ≥2b on digital subtraction angiography as well as the incidence of symptomatic intracerebral hemorrhage (sICH), and the favorable clinical outcome (modified Rankin scale [mRS] of 0-2) at 3 months after onset. Results: One-hundred and sixty-six patients (96 men; median age [interquartile range], 78 [69-85] years) were randomized 1:1 to either the early-E group or the late-E group. Twenty-three (13.9%) had proximal M1 occlusion; 60 (36.1%), distal M1 occlusion; 83 (50%), M2 occlusion. Early recanalization was similarly observed in the early-E group and in the late-E group (53.1% vs. 53.0%, P=1.000). The rate of significant recanalization was also similar between the 2 groups (27.2% vs. 33.7%, p=0.399). sICH was occurred in 4 (4.8%) patients in the early-E group and in 2 (2.4%) in the late-E group (p=0.682). Among the 144 patients who were pre-morbid mRS of 0-2 and eligible for 3 months assessment, favorable outcome was seen in 53.9% in the early-E group and 57.4% in the late-E group (p=0.738) Conclusions: The timing of the edaravone infusion should not affect the rate of early recanalization, sICH, or favorable outcome after t-PA therapy.


1985 ◽  
Vol 58 (1) ◽  
pp. 193-199 ◽  
Author(s):  
L. R. Snyder

Whereas it is widely believed that animals native to high altitude show lower O2 partial pressures at 50% hemoglobin saturation (P50) than do related animals native to low altitude, that “fact” has not been well documented. Consequently, P50 at pH 7.4, PCO2(7.4), the CO2 Bohr effect, and the buffer slope (delta log PCO2/delta pH) were determined via the mixing technique in Peromyscus maniculatus native to a range of altitudes but acclimated to 340 or 3,800 m. PCO2(7.4) and buffer slope were substantially lower at high altitude. The change in P50(7.4) between acclimation altitudes was minimal (0.8% increase at 3,800 m), because of counterbalancing changes in PCO2, 2,3-diphospho-D-glycerate concentration, and perhaps other factors. At both acclimation altitudes there was a highly significant negative correlation between P50(7.4) and native altitude. Since pH in vivo probably increases slightly at high altitude, the data on P50 corrected to pH 7.4 are probably underestimates of the difference in in vivo P50 at low vs. high altitude. Hence these results corroborate theoretical predictions that low P50 is advantageous under severe hypoxic stress.


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