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Increased systolic performance with diastolic dysfunction in adult spontaneously hypertensive rats
Oscar H Cingolani1, Xiao-Ping Yang, Maria A Cavasin
1Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
Insights
Spontaneously hypertensive rats (SHR) show enhanced systolic function but delayed relaxation and increased stiffness at 10-11 months, before heart failure (HF) develops. These findings in hypertensive heart disease models offer insights into early cardiac changes.
Area of Science:
- Cardiovascular Physiology
- Hypertensive Heart Disease Research
Background:
- Hypertensive heart disease (HHD) involves early cardiac hypertrophy and fibrosis, potentially leading to heart failure (HF).
- Heart failure (HF) manifests in spontaneously hypertensive rats (SHR) around 18 months of age.
- Early alterations in cardiac performance preceding overt HF in SHR remain incompletely understood.
Purpose of the Study:
- To investigate cardiac performance, including systolic and diastolic function, in 10- to 11-month-old SHR compared to normotensive Wistar-Kyoto rats (WKY).
- To assess whether cardiac hypertrophy in young SHR is associated with functional changes before the onset of heart failure.
Main Methods:
- Utilized a pressure-volume (PV) conductance catheter system for in vivo evaluation of cardiac function in SHR and WKY rats.
- Measured parameters of systolic function (e.g., preload recruitable stroke work [PRSW], +dP/dt) and diastolic function (e.g., time constant of relaxation [tau], end-diastolic pressure-volume relation [EDPVR]).
- Assessed ex vivo PV relations, Doppler E/A ratio, and plasma B-type natriuretic peptide (BNP) levels.
Main Results:
- SHR exhibited significantly enhanced systolic performance, indicated by higher PRSW, +dP/dt, and preload-adjusted maximal power (PWR(max)-EDV(2)).
- SHR demonstrated impaired diastolic function, characterized by a prolonged relaxation time constant (tau) and increased ventricular stiffness (EDPVR, ex vivo PV relation).
- Elevated Doppler E/A ratio and increased BNP levels in SHR suggest early cardiac stress and diastolic dysfunction.
Conclusions:
- At 10-11 months, prior to heart failure development, SHR display augmented systolic function.
- Concurrently, SHR exhibit delayed ventricular relaxation and increased diastolic stiffness, indicating early maladaptive changes in hypertensive heart disease.
- These findings highlight functional cardiac alterations in young SHR that precede overt heart failure, providing a model for studying early HHD pathophysiology.
Abstract:
Hypertensive heart disease is characterized by early development of hypertrophy and fibrosis that leads to heart failure (HF). HF develops in spontaneously hypertensive rats (SHR) after 18 months; however, it is not clear whether hypertrophy leads to altered cardiac performance at an earlier age in these rats. We studied cardiac performance in 10- to 11-month-old SHR and age-matched Wistar-Kyoto rats (WKY), using presssure-volume (PV) conductance catheter system to evaluate systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), +dP/dt, and its relation to end-diastolic volume (+dP/dt-EDV) and preload-adjusted maximal power (PWR(max)-EDV(2)) as well as the time constant of left ventricular pressure decay, tau (tau), as an index of relaxation. The slope of the end-diastolic pressure-volume relation (EDPVR) and the ex vivo PV relation, both indexes of stiffness, were also calculated for each heart, and the Doppler E/A ratio was determined. In addition, plasma samples were obtained to assess B-type natriuretic peptide levels (BNP). We found that PRSW was higher in SHR than in WKY (174.5+/-15.6 versus 92.6+/-18.9 mm Hg; P<0.01). +dP/dt and +dP/dt-EDV were also enhanced in SHR versus WKY (9125+/-662 versus 6633+/-392 mm Hg/sec, P<0.01, and 28.14+/-4.35 versus 12.7+/-2.8 mm Hg/s per micro L, P<0.02). In addition, PWR-EDV(2) was elevated in SHR (7.3+/-1.5 versus 3.1+/-0.6 mW/ micro L(2)). Tau was prolonged in SHR (14.5+/-1 ms versus 10.8+/-0.8 for WKY, P<0.02) and EDPVR was significantly greater in SHR than in WKY (0.01+/-0.005 versus 0.004+/-0.001, P<0.05). The ex vivo pressure-volume relation was also steeper for SHR and the E/A ratio was 2.53+/-0.15 for SHR versus 1.67+/-0.08 for WKY (P<0.02). BNP was 45+/-2.5 pg/mL for SHR and 33.3+/-1.8 pg/mL for WKY (P<0.02). Taken together, these data suggest that at 10 to 11 months of age, before HF develops, SHR have increased systolic performance accompanied by delayed relaxation and increased diastolic stiffness.