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Factors involved in delaying the rise in peripheral resistance in developing heart failure
K Kiuchi1, R P Shannon, N Sato
1Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston 02115.
Insights
Heart failure (HF) development shows severe contractile dysfunction before reduced cardiac output (CO) and a delayed rise in total peripheral resistance (TPR). This TPR increase stems from reduced vascular tone, not neurohumoral activation.
Area of Science:
- Cardiovascular Physiology
- Heart Failure Pathophysiology
- Vascular Biology
Background:
- Peripheral vascular control is crucial in heart failure (HF).
- Understanding the temporal sequence of cardiovascular changes in HF is essential for developing effective treatments.
- Neurohumoral activation is a known response to HF, but its role in peripheral vascular resistance is complex.
Purpose of the Study:
- To investigate the development of peripheral vascular control during pacing-induced heart failure in conscious dogs.
- To determine the sequence of changes in cardiac output (CO), left ventricular (LV) function, and total peripheral resistance (TPR) in developing HF.
- To explore the mechanisms underlying the changes in TPR, including intrinsic vascular tone and neurohumoral influences.
Main Methods:
- Measurements of CO, LV dP/dt, LV end-diastolic pressure, and arterial/right atrial pressures in 10 conscious dogs with pacing-induced HF.
- Assessment of plasma norepinephrine and renin activity at different stages of HF.
- In vitro studies on isolated femoral artery segments to evaluate intrinsic tone and intracellular calcium levels.
Main Results:
- Severe LV contractile dysfunction (decreased LV dP/dt, increased LV end-diastolic pressure) occurred by 3 weeks, preceding a drop in CO.
- CO significantly decreased at 4-7 weeks, but total peripheral resistance (TPR) did not increase, despite elevated plasma norepinephrine and renin activity.
- Isolated femoral arteries from HF dogs showed reduced intrinsic tone compared to controls, with no alteration in intracellular calcium levels.
Conclusions:
- In pacing-induced HF, severe LV contractile dysfunction precedes the decline in CO.
- The rise in TPR is delayed and occurs after the fall in CO, despite significant neurohumoral activation.
- Reduced intrinsic peripheral vascular tone, rather than increased vascular resistance, characterizes the vascular response in this model of HF.
Abstract:
The development of heart failure (HF) on peripheral vascular control was studied in 10 conscious dogs with measurements of cardiac output (CO) and left ventricular (LV), arterial, and right atrial pressures. At 3 wk after pacing-induced HF, CO was not decreased from 2.5 +/- 0.2 l/min, whereas LV dP/dt fell (from 2,858 +/- 71 to 1,409 +/- 69 mmHg/s) and LV end-diastolic pressure increased (from 4.8 +/- 0.4 to 27.3 +/- 1.1 mmHg) (P < 0.05). At 4-7 wk after pacing, CO was significantly decreased (to 1.6 +/- 0.1 l/min; P < 0.05), but total peripheral resistance (TPR) did not rise, despite increases in plasma norepinephrine and renin activity (P < 0.05). In the presence of ganglionic blockade, TPR was still not increased in HF. In vitro studies in isolated femoral artery segments demonstrated reduced intrinsic tone (0.028 +/- 0.007 g/mg; P < 0.05) as compared with vessels from sham-operated controls (0.124 +/- 0.023 g/mg), whereas the intracellular calcium level was not altered in HF. Thus, during the development of HF, severe contractile dysfunction precedes the fall in CO, which, in turn, precedes the rise in TPR. The delayed rise in TPR appears to involve a reduction in intrinsic peripheral vascular tone, despite neurohumoral activation.