Beneficial effects of intracoronary nicardipine on hypoxic myocardium.

Regional effects of intracoronary administration of nicardipine, a dihydropyridine derivative with calcium blocking activity, were studied in 13 open-chest dogs. Hypoxic, constant-flow perfusion was done in the area supplied by the distal left anterior descending artery. The 5-min regional hypoxic perfusion did not result in significant alterations in either heart rate or aortic pressure in 6 control dogs perfused with original Krebs-Henseleit solution (KHS), which was deoxygenized by mixed gas (95%N2 and 5%CO2), and in 7 dogs perfused with nicardipine-containing (0.2 mg/dl) KHS. A transmural biopsy after 5 min of perfusion revealed a less severe metabolic deterioration in nicardipine-treated dogs than in control dogs, as indicated by a higher ATP content (2.84 +/- 0.43 vs. 2.23 +/- 0.45 mumol/g, wet weight). The sequence of regional contractile deterioration was not different between the 2 groups. In conclusion, regional nicardipine administration showed a myocardial protective effect which was not mediated by afterload reduction in the whole heart.

Examination of the direct effects of antianginal agents on the hypoxic canine myocardium.

The myocardial protective effect of nicorandil, N-(2-hydroxyethyl) nicotinamide nitrate ester, against hypoxia was examined in comparison with that of nitroglycerin in 22 open chest dogs. The regional ventricular myocardium was perfused for 5 min with a hypoxic solution in 8 dogs (Group 1), with a hypoxic solution containing 0.5 or 2.5 mg/dl of nicorandil in 7 dogs (Group 2) and with a hypoxic solution containing 0.5 mg/dl of nitroglycerin in 7 dogs (Group 3). In Group 2, the ATP content of the hypoxic myocardium was 3.14 +/- 0.37 mumol/g, which was less than that in the uninvolved myocardium (4.31 +/- 0.57 mumol/g) but significantly higher than those of the hypoxic myocardium in Groups 1 and 3 (2.09 +/- 0.45 and 2.39 +/- 0.33 mumol/g, respectively). The lactate content of the hypoxic myocardium in Group 2 (5.05 +/- 1.13 mumol/g) was less than those of the hypoxic myocardium in Groups 1 and 3 (8.77 +/- 2.34 and 8.98 +/- 2.08 mumol/g, respectively). This protective effect was not caused by the hemodynamic changes. In contrast, nitroglycerin did not show any protective effects on the hypoxic myocardium.

[Contraction of the interventricular septum in right ventricular overload studied by two-dimensional echocardiography].

This study clarified the relationship between right ventricular (RV) overload and contraction of the interventricular septum using two-dimensional echocardiography. Seventeen patients with atrial septal defect (RV systolic pressure: 36 +/- 14 mmHg), 13 with mitral stenosis (49 +/- 19 mmHg), nine with primary pulmonary hypertension (87 +/- 21 mmHg) and 17 normal subjects (23 +/- 3 mmHg) were evaluated using two-dimensional echocardiography and cardiac catheterization. The circumferential lengths of the septum (Civs) and the left ventricular (LV) free wall (Cfw) were measured in the LV short-axis view at the level of the papillary muscles. In normal subjects, Civs was 3.4 +/- 0.5 cm and Civs/Cfw was 0.40 +/- 0.07. All patients with RV overload had longer Civs and greater Civs/Cfw as compared with the normal subjects. There was no significant difference in the Cfw among the cases with mitral stenosis and primary pulmonary hypertension and the normal subjects. Cfw in atrial septal defect was shorter than in the normal subjects. The percent contraction of Civs was decreased in mitral stenosis and primary pulmonary hypertension as compared with the normal subjects. No significant difference was found in the percent contraction of Civs between the normal subjects and the 11 patients with atrial septal defect with normal RV systolic pressure. However, in six patients with atrial septal defect with high RV systolic pressure, the percent contraction of Civs was decreased. There was an inverse correlation between RV systolic pressure and the percent contraction of Civs (r = -0.39, p less than 0.01), and RV ejection fraction (r = -0.52, p less than 0.01) defined by multiplegated equilibrium scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

Examination of the direct effects of nicorandil, verapamil, propranolol, and nitroglycerin on the hypoxic canine myocardium.

Effects of intracoronary administration of verapamil (VER), nitroglycerin (TNG), propranolol (PRO), and nicorandil (NIC) on regional hypoxia were examined in 39 open-chest dogs. Distal left anterior descending coronary artery was perfused for 5 min with deoxygenated Krebs-Henseleit solution (KHS) in group 1 (n = 9), VER-containing (1.3 mg/dl) KHS in group 2 (n = 9), TNG-containing (0.5 mg/dl) KHS in group 3 (n = 7), PRO-containing (0.4 or 0.8 mg/dl) KHS in group 4 (n = 7), and NIC-containing (0.5 or 2.5 mg/dl) KHS in group 5 (n = 7). Transmural biopsy at 5 min revealed a less severe metabolic deterioration in the hypoxic myocardium in groups 2, 4, and 5, as evidenced by higher ATP content (2.99 +/- 0.73, 2.81 +/- 0.35, and 3.14 +/- 1.20 mumol/g in groups 2, 4, and 5, respectively) and lower lactate accumulation (5.16 +/- 0.59, 5.62 +/- 1.44, and 5.05 +/- 1.12 mumol/g in groups 2, 4, and 5, respectively) compared with those in group 1 (2.09 +/- 0.45 mumol/g in ATP and 8.77 +/- 2.34 mumol/g in lactate). Metabolic preservation by VER, PRO, and NIC were not mediated by changes in hemodynamics and regional myocardial contraction. On the other hand, any significant protective effects were not noted in group 3, despite a significant reduction in rate-pressure products. Under an aerobic condition these agents affected regional myocardial contraction in a different manner from each other.

Comparative effects of intracoronary administration of propranolol with systemic administration on hypoxic canine myocardium.

Myocardial protective effects of intracoronary administration of relatively small doses of propranolol were examined and compared with systemic administration in 20 open-chest dogs. In group 1 (n = 6) rate-pressure-product (R X P) did not change during 5-minute left anterior descending artery (LAD) perfusion with deoxygenated Krebs-Henseleit solutions (KHS). However, R X P decreased by the same degree in group 2 (n = 7), which received perfusion with KHS containing 0.4 or 0.8 mg/dl of propranolol, and in group 3 (n = 7) given LAD perfusion with original KHS and systemic administration of 0.02 to 0.04 mg/kg of propranolol. Total administered doses of propranolol were the same for groups 2 and 3. Transmural biopsy after 5 minutes of perfusion revealed less severe metabolic deterioration of hypoxic myocardium in group 2 when compared with that in group 1, as evidenced by higher ATP (adenosine triphosphate) (2.81 +/- 0.35 versus 2.23 +/- 0.45 mumol/g, p less than 0.05) and lower lactate content (5.62 +/- 1.44 versus 9.01 +/- 2.62 mumol/g, p less than 0.05). On the other hand, significant metabolic preservation was not noted in group 3. Sequential changes in regional myocardial contraction did not differ among the three groups. In conclusion, intracoronary administration of propranolol showed myocardial protective effects that were not mediated by the changes in hemodynamics and myocardial contraction.

Changes in left ventricular diastolic function after left ventriculography: a comparison with iopamidol and urografin.

Changes in left ventricular (LV) diastolic indices after left ventriculography (LVG) with iopamidol or urografin were studied in 42 subjects. Increase in heart rate and decrease in LV systolic pressure were more significant with urografin than with iopamidol (p less than 0.05 to 0.001). LV end-diastolic pressure was elevated more with urografin than with iopamidol (p less than 0.005 to 0.05) 1 to 3 minutes after LVG. LV peak negative dP/dt decreased significantly with urografin immediately (10 to 15 seconds, -511 and 30 seconds, -376 mm Hg/sec; p less than 0.0005 to 0.02), but with iopamidol it did not decrease significantly after LVG. Time constant, T, was elongated with iopamidol (10 to 15 seconds, +13 and 30 seconds, +6 msec; p less than 0.0005), but this elongation was significantly less than urografin (10 to 15 seconds, +34; 30 seconds, +25; 1 minute, +15; and 2 minutes, +10 msec; p less than 0.05 to 0.0005). We conclude that iopamidol disturbed LV diastolic function to a lesser degree than did urografin.