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ATP‐Sensitive Potassium Channels Contribute to Progressive Coronary Vasodilation in Response to Acute Isovolemic Hemodilution
Author(s) -
Kiel Alexander M,
Goodwill Adam G,
Barnard April L,
Sturek Joshua T,
Noblet Jillian N,
Sassoon Daniel J,
Tune Johnathan D
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.836.19
Subject(s) - hematocrit , vasodilation , medicine , blood pressure , mean arterial pressure , anesthesia , heart rate , cardiology , chemistry
This study was designed to identify mechanisms responsible for coronary vasodilation in response to progressive decreases in arterial oxygen content. 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 synthetic plasma expander (Hespan, 6% hetastarch in 0.9% sodium chloride) up to a total sequential volume exchange of 4.02 ± 0.19 L. Arterial blood pressure, heart rate, left anterior descending coronary blood flow, and coronary arterial and venous blood gases were measured following stabilization after each fluid exchange. To establish content dependent effects, data were analyzed based on binned arterial oxygen contents of 18.0–13.0, 12.9–10.0, 9.9–8.0, 7.9–6.0, 5.9–4.0 ml O 2 /dl. Despite eliciting no change in mean arterial pressure, heart rate, or myocardial oxygen consumption, progressive hemodilution demonstrated clear reductions in arterial oxygen content (14.7 ± 0.4 to 4.7 ± 0.1 ml O 2 /dl; P < 0.001) and hematocrit (32 ± 1 to 10 ± 1%; P < 0.001). An accompanying increase in coronary flow was observed (0.39 ± 0.05 to 1.63 ± 0.16 ml/min/g; P < 0.001) which was sufficient to maintain oxygen delivery (58 ± 7 to 76 ± 8 μl O 2 /min/g; P = 0.46). Inhibition of nitric oxide synthase (L‐NAME: 25 mg/kg, iv) resulted in significant increases in mean arterial pressure (87 ± 2 to 122 ± 3 mmHg; P < 0.001) and myocardial oxygen consumption (47 ± 2 to 57 ± 3 μl O 2 /min/g; P < 0.001), however, this treatment did not significantly alter the coronary response to progressive anemia (P = 0.41). Inhibition of K V channels (4‐aminopyridine: 0.3 mg/kg, iv) also did not significantly alter coronary responses to decreasing arterial oxygen content. Alternatively, blockade of K ATP channels with glibenclamide (3 mg/kg, iv) significantly reduced the coronary blood flow response from 1.87 ± 0.11 ml/min/g to 1.12 ± 0.08 ml/min/g (P < 0.001) when arterial oxygen content was lowered from 15.1 ± 0.3 to 4.7 ± 0.1 ml O 2 /dl. This glibenclamide‐induced decrease in coronary flow diminished myocardial oxygen delivery from 69.4 ± 4.3 to 52.0 ± 4.3 μl O 2 /min/g (P < 0.001). Taken together, these data support that K ATP channels, but not K V channels or nitric oxide, contribute to coronary vasodilation in response to progressive, acute isovolemic hemodilution. Support or Funding Information This study was supported by U01HL118738 and the Purdue University Ross Fellowship. Ms. Noblet was supported by TL1 TR000162 (A. Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.