Key result
Absence of Kv1.5 channels in mice resulted in significantly lower baseline myocardial oxygen tension (20.1 vs 32.7 mmHg) and a decrease during norepinephrine infusion compared to wild-types.
Why the study?
Does the absence of Kv 1.5 channels impair myocardial oxygen tension regulation during increased cardiac workload in mice?
Does the absence of Kv 1.5 channels impair myocardial oxygen tension regulation during increased cardiac workload in mice?
Kv 1.5 channels play a critical role in coupling coronary blood flow to cardiac work, and their absence leads to tissue hypoxia and acute cardiac dysfunction during increased oxygen demand.
Answers are grounded in this paper and cite their sources.
Impaired myocardial oxygenation during stress in Kv1.5-deficient mice; leaves open whether channel modulation influences human coronary flow reserve.
The major “job” of the coronary circulation is to deliver oxygen and nutrients to the myocardium in a manner to match the myocardial demands under various conditions. Oxygen extraction in the coronary circulation is 70-80 % under resting conditions, which leaves very little reserve for further extraction. Because extraction is near maximum, to increase oxygen delivery further extraction is not a viable option. Previously, we found that Kv 1.5 channels appeared to couple cardiac work to myocardial blood flow. Specifically, we found reduced levels of flow per unit of cardiac work in mice null for the redox sensing Kv1.5 channel (Kv1.5-/-) compared to wild types (Wt). Based on these observations, we hypothesized that myocardial oxygen tension (pO2) at different cardiac workloads is lower in Kv 1.5-/- mice than in wild-type mice. For pO2 measurements, oxygen-sensing paramagnetic probes (LiNc-BuO:PDMS chip) were implanted into the left ventricular wall. After 2 weeks of implantation, pO2 was measured by using L-band (1.2 GHz) spectrometer. Measurements were done both at baseline and during norepinephrine (NE, 5µg/kg/min, iv. for 3 minutes) injection. Our results showed that at baseline pO2 in Kv 1.5-/- was significantly lower (20.1±4 mmHg) compared to Wt mice (32.7±2 mmHg). During NE infusion pO2 decreased in Kv 1.5-/- (14±4.6mmHg) whereas in Wt animals pO2 increased during NE (36±4.6mmHg (figure A,B). Based on these data, we conclude that Kv 1.5 channels play important role in coronary blood flow regulation and maintenance of myocardial oxygen tension. In the absence of Kv1.5 channels, when oxygen demands are incurred, tissue hypoxia results leading to acute cardiac dysfunction.
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Ohanyan et al. (2015) studied Myocardial oxygen balance. Kv1.5 channel knockout vs. Wild-type mice was evaluated on Myocardial oxygen tension (pO2) at baseline. Absence of Kv1.5 channels in mice resulted in significantly lower baseline myocardial oxygen tension (20.1 vs 32.7 mmHg) and a decrease during norepinephrine infusion compared to wild-types.
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