Rationale In the working heart coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels, which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox sensitive. Objective To determine the role of redox-sensitive Kv1.5 channels in coronary metabolic flow regulation. Methods and Results In mice (wild type [WT], Kv1.5 null [Kv1.5−/−], and Kv1.5−/− and WT with inducible, smooth muscle specific expression of Kv1.5 channels) we measured mean arterial pressure (MAP), myocardial blood flow (MBF), myocardial tissue pO2, and ejection fraction (EF) before and after inducing cardiac stress with norepinephrine (NE). Cardiac work (CW) was estimated as the product of MAP and heart rate. Isolated arteries were studied to establish if genetic alterations modified vascular reactivity. Despite higher levels of CW in the Kv1.5−/− (versus WT at baseline and all doses of NE), MBF was lower in Kv1.5−/− than in WT. At high levels of CW, tissue pO2 dropped significantly along with EF. Expression of Kv1.5 channels in smooth muscle in the null background rescued this phenotype of impaired metabolic dilation. In isolated vessels from Kv1.5−/− mice, relaxation to H2O2 was impaired, but responses to adenosine and acetylcholine were normal compared to WT. Conclusions Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism. Absence of these channels disassociates metabolism from flow resulting in cardiac pump dysfunction and tissue hypoxia.

Objective The connection between metabolism and flow in the heart, metabolic dilation, is essential for cardiac function. We recently found redox-sensitive Kv1.5 channels play a role in coronary metabolic dilation; however, more than one ion channel likely plays a role in this process since animals null for these channels still showed limited coronary metabolic dilation. Accordingly, we examined the role of another Kv1 family channel, the energetically-linked Kv1.3 channel, in coronary metabolic dilation. Methods We measured myocardial blood flow (contrast echocardiography) during norepinephrine-induced increases in cardiac work (heart rate × mean arterial pressure) in wild type mice (WT), WT mice given correolide (preferential Kv1.3 antagonist), and Kv1.3 null mice (Kv1.3−/−). We also measured relaxation of isolated small arteries mounted in a myograph. Results During increased cardiac work, myocardial blood flow was attenuated in Kv1.3−/− and in correolide-treated mice. In isolated vessels from Kv1.3−/− mice, relaxation to H2O2 was impaired (vs WT), but responses to adenosine and acetylcholine were equivalent to WT. Correolide reduced dilation to adenosine and acetylcholine in WT and Kv1.3−/−, but had no effect on H2O2-dependent dilation in vessels from Kv1.3−/− mice. Conclusion Kv1.3 channels participate in the connection between myocardial blood flow and cardiac metabolism.

Background and aims Takotsubo syndrome (TTS) is a conundrum without consensus about the cause. In a murine model of coronary microvascular dysfunction (CMD), abnormalities in myocardial perfusion played a key role in the development of TTS. Methods and results Vascular Kv1.5 channels connect coronary blood flow to myocardial metabolism and their deletion mimics the phenotype of CMD. To determine if TTS is related to CMD, wild-type (WT), Kv1.5−/−, and TgKv1.5−/− (Kv1.5−/− with smooth muscle-specific expression Kv1.5 channels) mice were studied following transaortic constriction (TAC). Measurements of left ventricular (LV) fractional shortening (FS) in base and apex, and myocardial blood flow (MBF) were completed with standard and contrast echocardiography. Ribonucleic Acid deep sequencing was performed on LV apex and base from WT and Kv1.5−/− (control and TAC). Changes in gene expression were confirmed by real-time-polymerase chain reaction. MBF was increased with chromonar or by smooth muscle expression of Kv1.5 channels in the TgKv1.5−/−. TAC-induced systolic apical ballooning in Kv1.5−/−, shown as negative FS (P < 0.05 vs. base), which was not observed in WT, Kv1.5−/− with chromonar, or TgKv1.5−/−. Following TAC in Kv1.5−/−, MBF was lower in LV apex than in base. Increasing MBF with either chromonar or in TgKv1.5−/− normalized perfusion and function between LV apex and base (P = NS). Some genetic changes during TTS were reversed by chromonar, suggesting these were independent of TAC and more related to TTS. Conclusion Abnormalities in flow regulation between the LV apex and base cause TTS. When perfusion is normalized between the two regions, normal ventricular function is restored.

We aimed to acquaint the reader with a medieval physician, Amirdovlat Amasiatsi, who lived and practiced in the 15th century Anatolia. Amirdovlat wrote several books on medicine mainly focusing on phytotherapy and pharmacology using medicinal plants, animal-derived products and minerals. All his works were written in Middle Armenian, spoken Armenian language of the time. In his writings, Amirdovlat described unique recipes that represent a portrayal of medical knowledge and practice at the time in Anatolia where he lived and worked. He discussed the physical and therapeutic properties as well as geographic distributions of various plants and minerals, using different languages, mainly Turkish, Greek, Arabic, French and Persian. Amirdovlat's works not only enhanced our understanding of Armenian medical practices but also provided great deal of information on those of Ancient Greco-Roman as well as Islamic world, demonstrating close relationship of Armenian medicine with Greco-Roman and Islamic medicine. Amirdovlat accomplished this by amalgamating the past and contemporary practices of his time. In this regard, Amirdovlat's works, in particular "Useless for the Ignorant", are very unique playing a significant role in preserving traditions and heritage of different cultures.