Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels

Alexander M. Kiel, Adam G. Goodwill, Jillian N. Noblet, April L. Barnard, Daniel J. Sassoon, Johnathan D. Tune

Research output: Contribution to journalArticle

8 Scopus citations

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+ (KV) channels (4-aminopyridine: 0.3 mg/kg iv; P = 0.52). However, administration of the KATP 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 (KATP) 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 KV channels.

Original languageEnglish (US)
Article number65
JournalBasic Research in Cardiology
Volume112
Issue number6
DOIs
StatePublished - Nov 1 2017

Keywords

  • Anemia
  • Coronary
  • K channels
  • K channels
  • Nitric oxide
  • Swine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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