Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart

Figures

• 

  FIGURE 1. Effects of glucagon upon cardiac contraction and contractile recovery from ischaemia/reperfusion. (a) Percentage of pre‐administration left ventricular developed pressure, (b) heart rate (bpm), and (c) percentage of pre‐administration rate‐pressure product during aerobic perfusion and following ischaemia/reperfusion. At 12 min before the induction of ischaemia, hearts were administered either 40 nM glucagon or vehicle control. RPP was calculated as LVDP multiplied by heart rate. Significance, as determined by the Welch's ANOVA and post‐hoc Welch's correction, is denoted on the graph for the three 5‐minute periods at the end of reperfusion, and the 10 min prior to induction of ischaemia. Data are mean ± SD; n = 3 hearts per group. LVDP, left ventricular developed pressure; RPP, rate–pressure product; SD, standard deviation.

• 

  FIGURE 2. Contractile effects of coadministration of glucagon with exenatide. (a) Percentage of pre‐administration of LVDP, (b) heart rate (bpm), and (c) percentage of pre‐administration RPP during aerobic perfusion and following ischaemia/reperfusion. At 12 min before induction of ischaemia, hearts were administered either 5 nM exenatide alone or in combination with 40 nM or 200 nM glucagon or vehicle control. RPP was calculated as LVDP multiplied by heart rate. Significance, as determined by the Welch's ANOVA and post‐hoc Welch's correction, is denoted on the graph for the three 5‐min periods at the end of reperfusion, and the 10 min prior to induction of ischaemia. Blue represents post‐hoc significance of 5 nM exenatide relative to vehicle; green represents post‐hoc significance of 200 nM glucagon plus 5 nM exenatide relative to 5 nM exenatide. (d) Represents the mean recovery of LVDP, heart rate, and RPP averaged across the 5‐min period before 96 min perfusion time. *p < 0.05, **p < 0.01, and ***p < 0.001. Red represents post‐hoc significance of 40 nM glucagon relative to vehicle, blue represents post‐hoc significance of 5 nM exenatide relative to vehicle, and green represents post‐hoc…

• 

  FIGURE 3. Duration of the contractile effects of glucagon. (a) LVDP (mmHg), (b) heart rate (bpm), and (c) RPP (mmHg.bpm) over 30 min aerobic perfusion without glucagon, and 34 min aerobic perfusion with 40 nM glucagon in the perfusion buffer. (d) Example trace showing left ventricular pressure (mmHg) before and after 40 nM glucagon administration. RPP was calculated as LVDP multiplied by heart rate. Exact statistical significance is annotated on the graph as relative to the 5‐min period before glucagon administration, as determined by the Student's t‐test for each subsequent 5‐min period following compound administration. Data are represented as mean ± SD; n = 6 hearts. bpm, beats per minute; LVDP, left ventricular developed pressure; RPP, rate–pressure product; SD, standard deviation.