Kazutane Usui

Effects of bunazosin, a selective α1-blocking agent, and propranolol used alone and in combination on canine ventricular refractoriness and its dispersion during myocardial ischemia

The individual and combined effects of bunazosin, a selective alpha 1-adrenergic blocking agent, and propranolol on ventricular refractoriness and its dispersion were assessed in 33 chloralose-anesthetized, sympathectomized, and vagotomized dogs 2-3 h after occlusion of the obtuse marginal branches of the circumflex artery. The refractory period was measured in eight sites of the ischemic zone, two sites of the border zone, and two sites of the normal zone with S1-S2 extrastimulus methods. In group 1 dogs (n = 9), coronary artery ligation significantly shortened refractoriness in the ischemic zone (p = 0.023-0.001 in each site). Intravenous (i.v.) administration of a low dose of bunazosin at 0.1 mg/kg significantly blunted the shortening of refractoriness in the ischemic zone (p = 0.026-0.002 in each site), although the values did not reach those observed in the nonischemic zones (both the border and normal zones), where refractoriness remained unchanged. In group 2 dogs (n = 11), a higher dose of i.v. bunazosin, 0.5 mg/kg, significantly blunted the shortening of the refractory period within the ischemic zone (from 149 +/- 14 to 175 +/- 8 ms; mean +/- SD, p < 0.001) and reached the levels of the nonischemic zones (border zone 175 +/- 15 ms, normal zone 170 +/- 14 ms), resulting in a dispersion reduction in refractoriness between the ischemic and nonischemic zones. This dispersion tended to increase again with i.v. administration of 0.2 mg/kg propranolol (ischemic vs. border zone p = 0.034; ischemic vs. normal zone p = 0.089).(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in Refractory-period Response of Canine Subendocardium and Subepicardium to Bunazosin, an α1-adrenoceptor Antagonist, and Propranolol During Myocardial Ischemia

Our objective was to investigate the effects of alpha1- or beta-adrenoceptor blockers on endocardial and epicardial refractory-period changes during myocardial ischemia in alpha-chloralose-anesthetized dogs. The first and second diagonal branches of the left anterior descending coronary artery were ligated. The refractory period was determined by an S1-S2 extrastimulus method. Dogs were treated with the alpha1-blocker bunazosin (0.1-0.2 mg/kg, i.v.; n = 16), the beta-blocker propranolol (0.2 mg/kg, i.v.; n = 15), or saline (n = 11). Dogs that developed ventricular tachycardia/fibrillation (VT/VF) during the experiment were excluded from the statistical assessment in refractory periods. In all groups, coronary ligation produced a significant shortening of the refractory period of ischemic epicardial tissue (p < 0.05) but only minimal shortening of ischemic endocardial refractory periods, resulting in an increased difference in repolarization time between the endo- and epicardial sites. Treatment with bunazosin ameliorated this ischemia-related shortening of refractory periods at both the endo- and epicardial sites, with a greater effect seen epicardially (p < 0.05), resulting in values similar to those in the nonischemic tissue. Treatment with propranolol prolonged refractory periods more in the epicardial (p < 0.01) than in endocardial sites, exacerbating the disparity in the refractory period between the endo- and epicardial sites (p < 0.05). Propranolol also prolonged the refractory period of nonischemic tissue (p < 0.05 and p < 0.01 in endo- and epicardial sites, respectively), resulting in a significant difference between the ischemic and normal myocardium at the endocardial site (p < 0.05). Results suggest that the alpha1-blocker bunazosin reduces the refractory-period disparity between the ischemic and normal myocardium without increasing the disparity between the endo- and epicardial surfaces, whereas propranolol produces a greater disparity.

Correlation of Coronary Artery Stenosis Site with Anterior or Inferior Projection of ST Changes Induced by Treadmill Exercise Using a Newly Devised 9-Lead Holter Method

A 9-lead Holter monitor using the lead-switching technique (9-lead DCG) and conventional 12-lead electrocardiograph (12-lead ECG) were simultaneously used for recording during treadmill exercise testing (Td-test) in 140 patients with coronary artery disease. Coronary arteriography was performed in 118 of the 140 patients, and the correlation between coronary stenosis and anterior or inferior projection of ST depressions occurring during the Td-test was investigated. Additionally, 10 patients with acute myocardial infarction (AMI) were studied to test ST elevation detection by the 9-lead DCG. The CM5 lead demonstrated ST depressions in 92 of the 109 patients showing ST depressions in one or more leads. High lateral (HL) and/or low lateral leads detected all ST depressions occurring in the I and aVL leads of the 12-lead ECG. Leads CM1, CM2 and CM3 exhibited low sensitivity (0-32%) and high specificity (56-100%), while leads CM4, CM5, and CM6 provided greater sensitivity (66-95%), but less specificity (3-32%) in detecting diseases of the left anterior descending artery, left circumflex artery and/or right coronary artery (RCA). In contrast, the low back (LB) lead demonstrated high sensitivity (88%) and high specificity (86%) in detecting RCA disease. Lead CM3 detected ST elevations in all 6 patients with anterior AMI, while the LB lead did so in all 4 patients with inferior AMI. With a Holter monitor, 4 leads are needed: CM5 like, CM3 like, lateral (such as HL) and inferior (such as LB). The LB lead is useful in detecting inferior ischemia.

Disproportional Response between Refractory Period and Blood Flow to α1- and β-Adrenoceptor Blockade in Canine Ischemic Myocardium

We investigated the response of refractory periods and blood flow to blockade of α1- and β-adrenoceptors alone, or in combination on endocardium and epicardium, during myocardial ischemia. Dogs were anesthetized with α-chloralose and divided into bunazosin (an α1-blocking agent)-treated (0.1–0.2 mg/kg, IV, n = 14), propranolol-treated (0.2 mg/kg, IV, n = 12), and vehicle-control (n = 10) groups. The diagonal branches of the left anterior descending artery were ligated. The refractory period (ERP) and blood flow (RMBF) were determined by an S1-S2 extrastimulus method and a nonradioactive microsphere technique, respectively. The duration of regional electrograms (DRE) was measured in the endocardial and epicardial sites. Bunazosin alone reversed the ischemia-related shortening of ERPs at both the endocardial and epicardial sites, with a greater effect seen epicardially (P < .05). Subsequent administration of propranolol further prolonged ERPs in both sites, although the effect was greater in the epicardial surface (P < .05). Bunazosin reduced RMBF to a greater degree at the endocardial site than at the epicardial site in the ischemic zone (P < .01 and P < .05, respectively), but the magnitude of the reduction in RMBF and the difference in RMBF between sites were similar to the control group (P < .01). Propranolol alone and subsequent administration of bunazosin prolonged the ERP more at the epicardial site (P < .01) than at the endocardial sites in the ischemic zone. Propranolol produced no significant difference in RMBF between both sites. DREs in animals treated with bunazosin and propranolol alone, or in combination, were similar to those in animals treated with vehicle. These results suggest that differences in ERPs between endocardium and epicardium with blockade of α1- and/or β-adrenoceptor are not due to concomitant alterations in RMBF, but to differences in electrophysiological properties of the endocardial and epicardial cells during the acute phase of myocardial ischemia.