Adaptation to acute pulmonary hypertension in pigs

Abstract

The extent of right ventricular compensation compared to the left ventricle is restricted and varies among individuals, which makes it difficult to define. While establishing a model of acute pulmonary hypertension in pigs we observed two different kinds of compensation in our animals. Looking deeper into the hemodynamic data we tried to delineate why some animals could compensate and others could not. Pulmonary hypertension (mean pressure 45 mmHg) was induced gradually by infusion of a stable thromboxane A₂ analogue U46619 in a porcine model (n = 22). Hemodynamic data (pressure-volume loops, strain-analysis of echocardiographic data and coronary flow measurements) were evaluated retrospectively for the short-term right ventricular compensatory mechanisms and limits (Roehl et al. [2012] Acta Anaesthesiol. Scand., 56:449-58) 10 animals showed stable arterial blood pressures, whereas 12 pigs exhibited a significant drop of 16.4 ± 9.9 mmHg. Cardiac output and heart rate were comparable in both groups. In contrast, right ventricular contractility and coronary flow only rose in the stable group. The unchanging values in the decrease group correlated with an increasing ST-segment depression and a loss of ventricular synchronism and resulted in a larger septum bulging to the right ventricle. Simultaneously, a reduced left-ventricular end-diastolic volume and a missing improvement in contractility in the posterior septal and inferior free wall of the left ventricle have been observed. Our findings suggest that right ventricular compensation during acute pulmonary hypertension is strongly dependent on the individual capability to increase coronary flow. The cause for inter-individual variability could be the dimension and reactivity of the coronary system.

Keywords: Coronary circulation; myocardial contraction; physiological adaptation; pulmonary hypertension; right; swine; ventricular dysfunction.

Figure 1

Influence of rising mean pulmonary artery pressure (mPAP) in both the stable group (SG) (n = 10) and the decrease group (DG) (n = 12) on (A) mean arterial pressure (mAP), (B) heart rate (HR) and (C) cardiac output (CO). P‐values within the figures were derived from ANOVA. Symbols mark significant differences between groups at the mPAP level (*<0.05; †<0.01; ‡<0.001).

Figure 2

Changes in (A), (B) end‐diastolic volume (Ved) and (C), (D) time of isovolumetric relaxation (Tau) in the left (LV) as well as in the right ventricle (RV) due to acute pulmonary hypertension (rising mean arterial pressure (mAP)) in the two different groups. P‐values within the figures were derived from ANOVA. Symbols mark significant differences between groups at the mPAP level (*<0.05; †<0.01; ‡<0.001).

Figure 3

Interventricular synchronization with augmenting mean pulmonary artery pressure (mPAP) in the different groups. (A) The increasing integral of the difference between right and left ventricular pressure (∫RVP‐LVP) reflects a loss of synchronization. (B) Systolic and (C) diastolic asynchronism are pictured separately. P‐values within the figures were derived from ANOVA. Symbols mark significant differences between groups at the mPAP level (*<0.05; †<0.01; ‡<0.001).

Figure 4

Different reactions to rising mean pulmonary artery pressures (mPAP) in the stable (SG) and the decrease group (DG) in (A) left (LV‐Ees) and (B) right ventricular end‐systolic elastance (RV‐Ees) as markers for contractility, (C) ST height, (D) diastolic (dias RCA flow) and (E) systolic right coronary artery flow (sys RCA flow) and (F) O₂ extraction. P‐values within the figures were derived from ANOVA. Symbols mark significant differences between groups at the mPAP level (*<0.05; †<0.01; ‡<0.001).

Figure 5

Analysis of echocardiographic left ventricular data of 17 animals: the change in the radial strain rate (SrR) [1/second] in a short axis in separate segments during rest (mean pulmonary artery pressure (mPAP) 20–25 mmHg) is illustrated and compared to pulmonary artery hypertension (mPAP 40–45 mmHg). Significant differences (*P < 0.05) between the two groups (A) Stable group; (B) Decrease group) were seen in the posterior septal wall as well as the inferior and posterior left ventricular free wall.