Related Experiment Videos
Importance of alpha 1-sympathetic activity for diurnal change in ischemic threshold in patients with stable angina
1College of Medical Technology, Kyoto University, Graduate School of Medicine, Japan.
Insights
Alpha-1 blockers, combined with calcium-channel blockers, significantly reduce morning-to-afternoon variations in coronary vascular resistance. This finding suggests alpha-1 sympathetic activity influences the diurnal changes in ischemic threshold for stable angina patients.
Area of Science:
- Cardiology
- Pharmacology
- Circadian Biology
Background:
- The mechanisms behind the diurnal variation in minimal coronary vascular resistance, leading to a lower ischemic threshold in the early morning, remain unclear.
- Understanding these mechanisms is crucial for managing conditions like stable angina.
Purpose of the Study:
- To investigate the effects of calcium-channel blockers (amlodipine) and alpha-1 blockers (prazosin) on the diurnal changes in ischemic threshold.
- To determine if these medications can mitigate the morning increase in minimal coronary vascular resistance.
Main Methods:
- A treadmill exercise test (Balke-Ware protocol) was performed on 15 stable angina patients in the morning and afternoon.
- Measurements were taken before and after administration of amlodipine alone and in combination with prazosin.
- Ischemic threshold was assessed by the reciprocal of minimal coronary vascular resistance, approximated using heart rate and blood pressure.
Main Results:
- Baseline minimal coronary vascular resistance was significantly higher in the morning than in the afternoon.
- Amlodipine alone did not eliminate this diurnal pattern.
- The addition of prazosin to amlodipine virtually abolished the diurnal difference in minimal coronary vascular resistance.
Conclusions:
- Alpha-1-sympathetic activity appears to play a significant role in the diurnal variation of the ischemic threshold in patients with stable angina.
- Combined alpha-1 and calcium-channel blockade may be beneficial in managing circadian variations in myocardial ischemia.
Background:
Although ischemic threshold reportedly is lower in the early morning than in the afternoon, the mechanisms that account for the diurnal change in minimal coronary vascular resistance in the potentially ischemic area are unknown.
Hypothesis:
We hypothesized that calcium-channel blockers and alpha 1 blockers may affect the ischemic threshold in the early morning and afternoon in patients with stable angina.
Methods:
Before and after the administration of the calcium antagonist amlodipine (5 mg) alone and combined with the alpha 1 blocker prazosin (1 mg), a treadmill exercise test using the Balke-Ware protocol was undertaken in the morning (8:00 A.M.) and repeated in the afternoon (1:00 P.M.) with 15 stable angina patients. The ischemic threshold was defined as a reciprocal of minimal coronary vascular resistance in the presence of comparable levels of myocardial ischemia indicated by 0.1 mV ST depression. Minimal coronary vascular resistance was calculated as mean blood pressure divided by coronary blood flow. Since the coronary blood flow is closely related to myocardial oxygen consumption, which can be replaced by the double product of heart rate and systolic blood pressure, minimal coronary vascular resistance was approximated to 1/heart rate.
Results:
At baseline, minimal coronary vascular resistance was significantly higher in the early morning than in the afternoon (8.5 +/- 0.3 x 10(-3) min/beats vs. 7.8 +/- 0.4 x 10(-3) min/beats, p < 0.01). Although treatment with amlodipine alone did not abolish the circadian pattern of minimal coronary vascular resistance (8.0 +/- 0.6 x 10(-3) min/beats vs. 7.7 +/- 0.6 x 10(-3) min/ beats, p < 0.05), the addition of prazosin virtually eliminated the diurnal difference in minimal coronary vascular resistance (7.4 +/- 0.5 x 10(-3) min/beats vs. 7.5 +/- 0.5 x 10(-3) min/beats, p = NS).
Conclusions:
These findings indicate that alpha 1-sympathetic activity may play a role in the pathogenesis of the diurnal change of ischemic threshold in patients with stable angina.