Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 12, Number 2, April 2021, pages 91-97

Combination of Linagliptin and Empagliflozin Preserves Cardiac Systolic Function in an Ischemia-Reperfusion Injury Mice With Diabetes Mellitus

Figure 1. Cardiac systolic parameters by Millar conductance catheter: (a) LV ejection fraction, (b) stroke volume, (c) cardiac index, (d) dP/dt, and (e) dV/dt were shown. LV: left ventricular; dP/dt max: the maximum peak time derivative of LV pressure; dP/dt min: the minimum peak time derivative of LV pressure; dV/dt max: LV volume at the peak LV filling rate; dV/dt min: LV volume at the peak LV ejection rate. The number of control, linagliptin, empagliflozin, and combination groups were 8, 7, 7, and 6, respectively. *P < 0.05; #P < 0.10 by one-way analysis of variance with post-hoc comparison using Dunnett’s test.

Figure 2. Representative photographs of picrosirius red-stained heart sections in (a) control, (b) linagliptin, (c) empagliflozin, and (d) combination groups were shown. (e) The ratios of fibrotic area per left ventricle were shown. The number of control, linagliptin, empagliflozin, and combination groups were 9, 10, 11, and 8, respectively. #P < 0.10 by one-way analysis of variance with post-hoc comparison using Dunnett’s test.

**Table 1.** Blood Glucose Level and Heart Weight/Body Weight
	Control (n = 6)	Linagliptin (n = 6)	Empagliflozin (n = 9)	Combination (n = 7)
P < 0.05, and ^aP < 0.10 by one-way analysis of variance with post-hoc* comparison using Dunnett’s test.
Blood glucose (mg/dL)
Day 0	397 ± 104	411 ± 106	441 ± 107	366 ± 79
Day 14	598 ± 201	494 ± 184	320 ± 78*	300 ± 157*
Day 35	660 ± 206	549 ± 180	478 ± 95^a	522 ± 85
Heart weight/body weight on day 35 (%)	0.53 ± 0.04	0.50 ± 0.03	0.47 ± 0.06	0.48 ± 0.07

Table 1. Blood Glucose Level and Heart Weight/Body Weight

Control (n = 6)

Linagliptin (n = 6)

Empagliflozin (n = 9)

Combination (n = 7)

*P < 0.05, and ^aP < 0.10 by one-way analysis of variance with post-hoc comparison using Dunnett’s test.

Blood glucose (mg/dL)

Day 0

397 ± 104

411 ± 106

441 ± 107

366 ± 79

Day 14

598 ± 201

494 ± 184

320 ± 78*

300 ± 157*

Day 35

660 ± 206

549 ± 180

478 ± 95^a

522 ± 85

Heart weight/body weight on day 35 (%)

0.53 ± 0.04

0.50 ± 0.03

0.47 ± 0.06

0.48 ± 0.07

**Table 2.** Millar Conductance Catheter Analyses Without LV Systolic Parameters
	Control (n = 8)	Linagliptin (n = 7)	Empagliflozin (n = 7)	Combination (n = 6)
LV: left ventricular; P max: maximum pressure; P min: minimum pressure; V max: maximum volume; V min: minimum volume; ESP: end-systolic pressure; ESV: end-systolic volume; EDP: end-diastolic pressure; EDV: end-diastolic volume; HR: heart rate; Ea: arterial elastance; tau: LV diastolic time constant.
P max (mm Hg)	91 ± 53	81 ± 8	75 ± 26	98 ± 38
P min (mm Hg)	10 ± 19	6 ± 6	5 ± 5	9 ± 4
V max (mL)	0.038 ± 0.009	0.041 ± 0.010	0.035 ± 0.009	0.048 ± 0.008
V min (mL)	0.027 ± 0.007	0.029 ± 0.007	0.024 ± 0.008	0.032 ± 0.009
ESP (mm Hg)	85 ± 54	78 ± 9	69 ± 27	94 ± 39
ESV (mL)	0.028 ± 0.008	0.030 ± 0.007	0.024 ± 0.008	0.034 ± 0.010
EDP (mm Hg)	11 ± 19	8 ± 6	6 ± 5	10 ± 5
EDV (mL)	0.037 ± 0.008	0.040 ± 0.008	0.035 ± 0.009	0.047 ± 0.008
HR (beats/min)	449 ± 44	471 ± 25	429 ± 41	459 ± 78
Ea (mm Hg/mL)	9,156 ± 5,541	7,344 ± 2,907	7,831 ± 5,494	5,564 ± 2,280
tau (ms)	16 ± 15	10 ± 3	13 ± 6	11 ± 6

Table 2. Millar Conductance Catheter Analyses Without LV Systolic Parameters

Control (n = 8)

Linagliptin (n = 7)

Empagliflozin (n = 7)

Combination (n = 6)

LV: left ventricular; P max: maximum pressure; P min: minimum pressure; V max: maximum volume; V min: minimum volume; ESP: end-systolic pressure; ESV: end-systolic volume; EDP: end-diastolic pressure; EDV: end-diastolic volume; HR: heart rate; Ea: arterial elastance; tau: LV diastolic time constant.

P max (mm Hg)

91 ± 53

81 ± 8

75 ± 26

98 ± 38

P min (mm Hg)

10 ± 19

6 ± 6

5 ± 5

9 ± 4

V max (mL)

0.038 ± 0.009

0.041 ± 0.010

0.035 ± 0.009

0.048 ± 0.008

V min (mL)

0.027 ± 0.007

0.029 ± 0.007

0.024 ± 0.008

0.032 ± 0.009

ESP (mm Hg)

85 ± 54

78 ± 9

69 ± 27

94 ± 39

ESV (mL)

0.028 ± 0.008

0.030 ± 0.007

0.024 ± 0.008

0.034 ± 0.010

EDP (mm Hg)

11 ± 19

8 ± 6

6 ± 5

10 ± 5

EDV (mL)

0.037 ± 0.008

0.040 ± 0.008

0.035 ± 0.009

0.047 ± 0.008

HR (beats/min)

449 ± 44

471 ± 25

429 ± 41

459 ± 78

Ea (mm Hg/mL)

9,156 ± 5,541

7,344 ± 2,907

7,831 ± 5,494

5,564 ± 2,280

tau (ms)

16 ± 15

10 ± 3

13 ± 6

11 ± 6