Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: Role of K+ channels
dc.contributor.author | Kiel, Alexander M. | |
dc.contributor.author | Goodwill, Adam G. | |
dc.contributor.author | Noblet, Jillian N. | |
dc.contributor.author | Barnard, April L. | |
dc.contributor.author | Sassoon, Daniel J. | |
dc.contributor.author | Tune, Johnathan D. | |
dc.contributor.department | Cellular and Integrative Physiology, School of Medicine | en_US |
dc.date.accessioned | 2018-04-24T17:06:27Z | |
dc.date.available | 2018-04-24T17:06:27Z | |
dc.date.issued | 2017-11 | |
dc.description.abstract | This study was designed to identify mechanisms responsible for coronary vasodilation in response to progressive decreases in hematocrit. Isovolemic hemodilution was produced in open-chest, anesthetized swine via concurrent removal of 500 ml of arterial blood and the addition of 500 ml of 37 °C saline or synthetic plasma expander (Hespan, 6% hetastarch in 0.9% sodium chloride). Progressive hemodilution with Hespan resulted in an increase in coronary flow from 0.39 ± 0.05 to 1.63 ± 0.16 ml/min/g (P < 0.001) as hematocrit was reduced from 32 ± 1 to 10 ± 1% (P < 0.001). Overall, coronary flow corresponded with the level of myocardial oxygen consumption, was dependent on arterial pressures ≥ ~ 60 mmHg, and occurred with little/no change in coronary venous PO2. Anemic coronary vasodilation was unaffected by the inhibition of nitric oxide synthase (l-NAME: 25 mg/kg iv; P = 0.92) or voltage-dependent K+ (K V) channels (4-aminopyridine: 0.3 mg/kg iv; P = 0.52). However, administration of the K ATP channel antagonist (glibenclamide: 3.6 mg/kg iv) resulted in an ~ 40% decrease in coronary blood flow (P < 0.001) as hematocrit was reduced to ~ 10%. These reductions in coronary blood flow corresponded with significant reductions in myocardial oxygen delivery at baseline and throughout isovolemic anemia (P < 0.001). These data indicate that vasodilator factors produced in response to isovolemic hemodilution converge on vascular smooth muscle glibenclamide-sensitive (K ATP) channels to maintain myocardial oxygen delivery and that this response is not dependent on endothelial-derived nitric oxide production or pathways that mediate dilation via K V channels. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Kiel, A. M., Goodwill, A. G., Noblet, J. N., Barnard, A. L., Sassoon, D. J., & Tune, J. D. (2017). Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels. Basic research in cardiology, 112(6), 65. https://doi.org/10.1007/s00395-017-0654-x | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/15902 | |
dc.language.iso | en | en_US |
dc.publisher | Springer | en_US |
dc.relation.isversionof | 10.1007/s00395-017-0654-x | en_US |
dc.relation.journal | Basic research in cardiology | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | Author | en_US |
dc.subject | coronary | en_US |
dc.subject | anemia | en_US |
dc.subject | nitric oxide | en_US |
dc.title | Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: Role of K+ channels | en_US |
dc.type | Article | en_US |