Inhibition of BKCanegatively alters cardiovascular function

Figure 1. Echocardiographic analysis of the heart. (A) Parasternal long‐axis view of the heart. (B) Short‐axis view of the heart. (C) Apical four‐chamber view of the heart. (D) Tracing the left ventricular myocardial borders for strain analysis. (E) Strain analysis indicating left ventricular volume (red) and derivative of tissue velocity (blue) wall motion in two cardiac cycles. The green line indicates the corresponding EKG. (F) Radial strain for two long‐axis LV contractions. (G) Longitudinal strain for two long‐axis LV contractions. Ao, aorta; AV, aortic valve; IVS, interventricular septum; LA, left atrium; LV, left ventricle; LVAW, left ventricular anterior wall; LVPW, left ventricular posterior wall; MV, mitral valve; PA, pulmonary artery; PV, pulmonic valve; RA, right atrium; RV, right ventricle; RVOT, right ventricular outflow tract; TV, tricuspid valve.

Figure 2. Change in heart rate (beats per minute) after administration of Paxilline or Iberiotoxin. (A) Absolute reduction in heart rate after administration of DMSO control compared with low‐dose and high‐dose Paxilline or Iberiotoxin at baseline (n = 5–7), 1 min, and 15 min after injection. (B) Fold change in heart rate from baseline for the three groups at 1 min and 15 min after injection. Treatment with Paxilline at low dose resulted in decreased heart rate at 1 and 15 min. At high doses, a decrease in heart rate was also seen. Treatment with the higher dose of Paxilline showed a greater fold reduction in heart rate at 15 min compared with the low‐dose Paxilline. The use of Iberiotoxin did not significantly affect the heart rate. (C) Representative mean arterial pressure traces with or without (50 ng/mL Paxilline, n = 4). (D) Percentage change of MAP normalized to MAP before Paxilline injection. There was no difference observed in the MAP with Paxilline as compared with the DMSO control.

Figure 3. Evaluation of left ventricular function after administration of Paxilline (n = 7) or Iberiotoxin (n = 4). (A) Bar graphs showing an absolute reduction in left ventricular ejection fraction. (B) Fold change in left ventricular ejection fraction obtained from A. (C) Bar graph showing changes in absolute global longitudinal strain values. (D) Fold change in global longitudinal strain calculated from C. No statistically significant reduction in left ventricular ejection fraction was found. Although not statistically significant, strain analysis revealed a trend toward reduction in left ventricular function seen with Paxilline at low and high doses at both 1 and 15 min after drug administration.

Figure 4. Evaluation of coronary flow after administration of Paxilline (n = 5) or Iberiotoxin (n = 4). (A) Absolute reduction in mean coronary velocity. (B) Absolute reduction in mean coronary gradient. (C) Fold change in mean coronary velocity. (D) Fold change in mean coronary gradient. Velocity through the left main coronary artery was found to be decreased 1 min after administration of high‐dose Paxilline. This reduction in flow normalized at 15 min. Mean coronary gradient in this particular group was also found to be decreased.

Figure 5. Evaluation of pulmonic artery and right heart function after administration of Paxilline (n = 5) or Iberiotoxin (n = 4). (A) Bar graph showing fold change in mean pulmonary velocity. (B) Bar graph representing fold change in mean pulmonary gradient. (C) Absolute change in pulmonary artery diameter. (D) Absolute change in right ventricular outflow tract diameter. Velocity across the pulmonic valve was decreased 1 min after administration of both low‐dose and high‐dose Paxilline. In both dosages, velocity began to show normalization by 15 min. Mean pulmonary gradient showed a similar trend. In both cases, Iberiotoxin did not show an effect. No differences were seen in pulmonary artery diameter and right ventricular outflow tract diameter.