Related Experiment Videos
Benefits of prolonged angiotensin-converting enzyme inhibition in congestive heart failure
1Department of Medicine, Tulane University School of Medicine, New Orleans, La.
Insights
Normal circadian rhythms regulate cardiovascular function. Congestive heart failure disrupts these rhythms, increasing heart workload and impacting therapy effectiveness.
Area of Science:
- Cardiovascular physiology
- Chronobiology
- Pharmacology
Background:
- Normal individuals exhibit daily (circadian) variations in heart rate, blood pressure, and neuroendocrine function.
- These physiological changes influence cardiac workload, with higher activity during waking hours and rest during sleep.
- Cardiovascular mortality and morbidity are linked to these natural variations.
Purpose of the Study:
- To examine the impact of lost circadian variations in congestive heart failure (CHF) on cardiac workload and exercise tolerance.
- To discuss the implications of these time-dependent pathophysiological changes for optimizing pharmacological therapy in CHF patients.
Main Methods:
- The study reviews existing literature on circadian variations in cardiovascular function and their alterations in CHF.
- It analyzes the effects of neurohumoral dysregulation and reduced blood flow to skeletal muscle in CHF patients.
- The implications for vasodilator therapy timing and efficacy assessment are discussed.
Main Results:
- CHF patients lose normal circadian blood pressure and heart rate variations, leading to elevated nighttime cardiac workload.
- Reduced ability to increase blood flow to exercising muscles limits exercise tolerance in CHF.
- Existing vasodilator therapies may have suboptimal effects due to these time-dependent factors.
Conclusions:
- Optimizing vasodilator therapy in CHF requires consideration of circadian rhythms to ensure continuous cardiac unloading.
- Therapy should also address factors limiting skeletal muscle blood flow to prevent intermittent exercise capacity compromise.
- Drug efficacy assessment in CHF must include analysis of peak and trough effects over the dosing interval.
Abstract:
Normal individuals have time-dependent variations in cardiovascular function, most of which are circadian (once daily). They include changes in heart rate, systemic arterial blood pressure, cardiac output, blood volume, and viscosity. There are also changes in neuroendocrine function, including the sympathetic and parasympathetic nervous systems and the renin-angiotensin system. These variations have important consequences for the heart, since haemodynamic and neuroendocrine alterations determine cardiac work load; heart rate, blood pressure, and sympathetic nervous system activity are highest during the waking hours and lowest during sleep. Cardiovascular mortality and morbidity are associated with these changes. Patients with congestive heart failure undergo changes in neurohumoral cardiovascular regulation that increase the work load of the heart as a result of increases in heart rate and peripheral vascular resistance. Moreover, a normal circadian variation is lost, causing blood pressure and heart rate to remain increased at night, depriving the heart of a period of rest. In addition, these patients have an ability to increase blood flow to exercising skeletal muscle, limiting exercise tolerance, as well as the consequences of elevated ventricular filling pressures. These time-dependent variations in the pathophysiological processes of congestive heart failure have implications for pharmacological therapy. In particular, vasodilator therapy should be administered to provide optimal unloading of the heart throughout the day. Vasodilator therapy should also provide antagonism to those factors that limit blood flow to working skeletal muscle, so that the physical ability is not intermittently compromised during the trough effect of the drug. Criteria for establishing the efficacy of drugs for the treatment of congestive heart failure should include an analysis of peak and trough effects.