Increased resting heart rate indicates high-workload hearts with augmented aortic hydraulic power in hypertensive pigs

Figures

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  Fig 1. AA coarctation-induced increases in blood pressure measured by both carotid intra-arterial and brachial cuff methods. Intra-arterial pressures (ABPs) measured from porcine carotid arteries (A-C): systolic (A), diastolic (B), and mean (C) before coarctation (Pre) and prior to sacrifice (Sac) at 4 weeks (4W), 8 weeks (8W) and 12 weeks (12W). Cuff pressures (CBPs) measured from porcine brachial arteries (D-F): systolic (D), diastolic (E), and mean (F) before coarctation (Pre) and prior to sacrifice (Sac) at 4, 8 and 12 weeks. Sham group, n = 7 (2F, 5M); 4W group, n = 4 (2F, 2M); 8W group, n = 4 (1F, 3M); 12W group, n = 4 (2F, 2M). Data are expressed as mean ± SD, compared to Sham group, * p <0.05, **p<0.01, ***p < 0.001; compared to pre-coarctation, +++ p < 0.001; compared to the 4W group, # p < 0.05; compared to the 8W group, $ p < 0.05. AAC: abdominal aorta coarctation, F: female, M: male.

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  Fig 2. Hemodynamic analyses of proximal abdominal aortas (AA) following AA coarctation for different time periods. Mean aortic pressure (A), mean blood flow rate (B), and heart rate (C) were measured in AA proximal to coarctation for pigs undergoing coarctation for 4 weeks (4w), 8 weeks (8w), and 12 weeks (12w) before (Pre) and after (Post) coarctation, and before sacrifice (Sac) using sham group as references. Resistance (D), hydraulic power (E), and hydraulic energy (F) were calculated as described in Methods. Sham group, n = 9 (3F, 6M); 4W group n = 4 (2F, 2M); 8W group, n = 5 (1F, 4M); 12W group n = 8 (2F, 6M). Values are expressed as mean ± SD, compared to Sham group, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p< 0.0001. F: female, M: male.

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  Fig 3. Hemodynamic analyses of proximal abdominal aortas in pigs exhibiting different aortic hydraulic powers. Mean aortic pressure (A), mean blood flow rate (B) and heart rate (C) were measured in the abdominal aorta (AA) proximal to coarctation for pigs undergoing AA coarctation before (Pre) and after (Post) coarctation, and before sacrifice (Sac). Resistance (D), hydraulic power (E), and hydraulic energy (F) were calculated as described in Methods. Values of sham group served as references. Pigs undergoing AA coarctation was clustered into two sub-groups based on the presence (Cluster 1) and absence (Cluster 2) of aortic hydraulic power increases at sacrifice. Sham group, n = 9 (3F, 6M); Cluster 1 group, n = 5 (2F, 3M); Cluster 2 group, n = 12, (3F, 9M). Values were expressed as mean ± SD, compared to Sham group, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001; compared to Cluster 1 group, + p < 0.05, ++++ p < 0.0001. F: female, M: male.

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  Fig 4. Cluster 1 pigs exhibited marked increases in both carotid arterial pressures and mean heart rate. Systolic arterial pressure (A), diastolic arterial pressure (B), mean arterial pressure (C), and mean heart rate (D) were measured in the right carotid artery for pigs undergoing abdominal aorta coarctation before (Pre) and after (Post) coarctation, and before sacrifice (Sac) using sham group as references. Sham group, n = 7 (2F, 5M); Cluster 1 group n = 4 (2F, 2M); Cluster 2 group, n = 8 (3F, 5M). Values were expressed as mean ± SD, compared to Sham group, * p < 0.05, ** p < 0.01, **** p < 0.0001; compared to Pre group, + p < 0.05, ++ p < 0.01, +++ p < 0.001; compared to cluster 2 group, ## p < 0.01, #### p < 0.0001. F: female, M: male.

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  Fig 5. Cardiomyocyte hypertrophy and myocardial fibrosis were not detected in the left ventricular (LV) wall following AA coarctation. Immunofluorescence was used to detect cardiomyocytes in tissue sections of the LV of sham (n = 8, 2F and 6M), Cluster 1 (n = 4, 1F and 3M), and Cluster 2 (n = 9, 3F and 6M) groups. Nuclear density of cardiomyocytes was calculated as the number of nuclei per unit area of cardiac myosin heavy chain-positive cells. Myocardial fibrosis in the LV wall was detected with Masson’s trichrome staining. Sham group, n = 6 (2F, 4M); Cluster 1 group, n = 3 (1F, 2M); Cluster 2 group, n = 4 (4M). A and B show representative results; C, D, and E summarize quantitative results of cross-sectional area (C), nuclear density (D), and Masson’s trichrome staining (E). Values were expressed as mean ± SD. F: female, M: male.

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  Fig 6. The expression of heat shock protein 40 was upregulated in the left ventricle (LV) of the Cluster 1 group. The expression levels of heat shock protein 90 (HSP90), HSP70, HSP60, HSP40, and osteopontin in the LV wall were detected with immunoblotting using α-tubulin as the loading control. A shows representative immunoblots and B-F summarize quantitative results of HSP90 (B), HSP70 (C), HSP60 (D), HSP40 (E), and osteopontin (F). Sham group, n = 9 (3F, 6M); Cluster 1 group, n = 4 (2F, 2M); Cluster 2 group, n = 11 (3F, 8M). Values are expressed as mean ± SD, * p < 0.05 Cluster 1 vs. Cluster 2. F: female, M: male.

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  Fig 7. Receiver operating characteristic (ROC) curves for prediction of sham, Cluster 1, and Cluster 2 groups with indicators hydraulic power (A), resistance (B), mean heart rate (C), and mean arterial pressure (D). The optimal values of sensitivity and specificity for each ROC curve, as indicated with circles, were selected based on the Youden index. AUC: area under ROC curve; Sen: sensitivity; Spe: specificity.