Importance of alpha 1-sympathetic activity for diurnal change in ischemic threshold in patients with stable angina.
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.


OBJECTIVE
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.
Fujita
M
M
College of Medical Technology, Kyoto University, Graduate School of Medicine, Japan.
Tanaka
T
T
Nakae
I
I
Tamaki
S
S
Kihara
Y
Y
Nohara
R
R
Sasayama
S
S
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002940:Circadian Rhythm; D004056:Differential Threshold; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology; D011224:Prazosin / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D017311:Amlodipine; D011224:Prazosin