Effect of celiprolol on cardiac hypertrophy in hypertension.

The present study was undertaken to clarify whether celiprolol and atenolol, beta1-selective beta blockers with and without intrinsic sympathomimetic activity (ISA), respectively, might improve ischemic damage in the isolated perfused hearts of spontaneously hypertensive rats (SHR), and whether long-term treatment with celiprolol may reduce left ventricular hypertrophy (LVH) in patients with essential hypertension. Atenolol (50 mg/kg/day) or celiprolol (300 mg/kg/day) for 7 weeks significantly reduced the blood pressure in SHR to the same degree, and both drugs decreased the heart rate, but the magnitude of the fall in heart rate was significantly higher with atenolol treatment than with celiprolol treatment. Both treatments significantly reduced the ratio of LV weight to body weight in SHR and significantly improved the coronary reserve in SHR to the same extent. Both treatments significantly improved the extent of recovery of the pressure-rate product and the extent of percent recovery of the coronary flow after reperfusion following 30 min of ischemia in SHR. Celiprolol treatment in patients with essential hypertension for 12 months significantly decreased interventricular septal thickness (IVST)+LV posterior wall thickness (PWT) and LV mass index (LVMI), but there was no significant correlation between IVST+PWT or LVMI and blood pressure before and after treatment. IVST+PWT and LVMI were significantly decreased after 3 months of treatment and these LVH indices were significantly smaller after 6 and 12 months of treatment than after 3 months of treatment. In conclusion, both celiprolol and atenolol treatment reduced LVH and improved the ischemic damage in SHR. In essential hypertensive patients with LVH, celiprolol treatment effectively reduced blood pressure and achieved LVH regression.

Efficacy of long-term treatment with nipradilol, a nitroester-containing beta-blocker, in patients with mild-to-moderate essential hypertension.

The effects of long-term treatment with nipradilol, a nitroester-containing beta-blocker, on casual and 24-hour blood pressures were studied in 70 patients with mild-to-moderate essential hypertension. Antihypertensive effects of nipradilol on casual blood pressure were observed in 68% of patients. Nipradilol reduced pulse rates, but no bradycardia was observed. The usefulness of nipradilol in the present study was 65%. The results of ambulatory blood pressure monitoring indicated that nipradilol reduced systolic blood pressure more than diastolic blood pressure, and reduced blood pressure during waking more than during sleep. These results suggest that nipradilol is a safe and useful long-term antihypertensive drug in both young and older patients with mild-to-moderate essential hypertension. When administered twice daily, nipradilol is effective throughout a 24-hour period.

[Effect of bisoprolol, a beta 1-selective beta-blocker, on lipid and glucose metabolism and quality of life in elderly patients with essential hypertension].

The present study investigated the effect of bisoprolol, a beta 1-selective beta-blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose metabolism and quality of life (QOL) in elderly patients with essential hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12 weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate essential hypertension. In both groups bisoprolol significantly decreased both systolic and diastolic blood pressures and significantly reduced pulse rates to the same extent. The levels of serum cholesterol, HDL-cholesterol and triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose load, were not changed in either group by the bisoprolol treatment. Bisoprolol significantly improved QOL in both groups. Bradycardia, a side effect attributable to bisoprolol, was noted in only one patient in the elderly group. These results suggest that bisoprolol is a safe and useful antihypertensive drug in elderly and non-elderly patients with essential hypertension.

[A case of right atrial myxoma--the availability of transesophageal echocardiography in the detection of right atrial myxoma].

A 72-year-old woman had experienced palpitation and fatigue during exertion for two months and was referred to our hospital from her nearby hospital. On physical examination, a systolic murmur was heard in the left fourth intercostal space. A chest X-ray film showed cardiac enlargement (CTR 64%). An ECG showed elevated P waves in leads II, III. Transthoracic echocardiography revealed a large oval heterogeneous mass in the right atrium. Transesophageal echocardiography (TEE) revealed the right atrial mass clearly, which was attached to the atrial septum with a short wide stalk. This mass prolapsed from the right atrium into the right ventricle in diastole. And there were some cysts in the homogeneous high-echoic lesion. The chest CT and MRI also showed the mass in the right atrium. However, these images were not clear. Surgical excision of the mass was undertaken. A solid mass measuring 75 x 50 x 45 mm was attached to the fossa ovalis with a wide short stalk. There were several cysts in the mass. Pathological examination showed myxomatous tissue. In this case, TEE was the most valuable means for evaluation of the right atrial mass.

Theoretical validity of predicting right ventricular systolic pressure by a quantitative index of interventricular septal displacement in acute right ventricular pressure overload.

A leftward shift of the interventricular septum (IVS) of the heart is observed in patients with right ventricular pressure overload (RVPO). We simulated the leftward displacement of IVS in a modified ellipsoidal model on the assumption that the IVS generates the same tension as the left ventricular (LV) free-wall in acute RVPO, and derived the relational equations between ventricular pressures (RVP, LVP) and eccentricity index (EI = LVAPD/LVSLD, LVAPD: left ventricular anterior-posterior diameter, LVSLD: left ventricular septal-lateral diameter). The equations indicate that RVP/LVP correlates with simultaneous EI, independent of the absolute LV wall tensions and the LV size. To confirm this result, we undertook recurrent pulmonary embolizations in anesthetized open-chest dogs, and analyzed the relationship between RVP/LVP and EI at four phases in systole through the course of RVPO and shock. The advance of RVPO shifted the peak of RVP toward late-systole and made the values of RVP/LVP and EI significantly greater at late-systole than at early-systole. There were significant linear relationships between instantaneous EI and RVP/LVP at each phase, expect for the early systole in the shock stage, and the regression lines on all phases were similar to one another. These results are consistent with our theoretical ones. Therefore we conclude that it is reasonable to predict RVP by using EI, theoretically and experimentally.

Deaths in early phase of acute myocardial infarction and approaches for reducing the in-hospital and out-hospital case-fatality rates of the disease.

Shiritsu Asahikawa Hospital received a total of 922 patients with acute myocardial infarction (AMI) from 1961 through 1985. The numbers of AMI patients and deaths during 1981-1985 were 2.8 times and 2.3 times, respectively, those observed during 1971-1975. However, decreasing trends were noted in the overall and age-adjusted mortality due to ischemic heart disease (IHD) per population of 100,000 Asahikawa residents between 1975 and 1984, suggesting a discrepancy between our CCU data and the city's records. We investigated the prehospital condition, out-of-hospital cardiac arrest, and the mechanism of early deaths in patients hospitalized with AMI. It was found that the increase of AMI patients admitted to our hospital was due to an increase in the hospitalization rate of AMI patients and the establishment of the coronary care unit (CCU) which allowed the admittance of patients who might have been declared dead out-of-hospital in the past. On the other hand, the declining trends in IHD mortality in the entire city of Asahikawa were attributable to reductions in the in-hospital and out-of-hospital fatality rates of patients with AMI, to improved hospital fatality rates of patients with AMI, and to improved survival rates in AMI patients who developed ventricular fibrillation (Vf) or who experienced out-of-hospital cardiac arrest episode. In order to further decrease the case-fatality rate of patients with AMI, it is essential to continuously educate residents on emergency treatment to be given at the onset of AMI.

[Left ventricular behavior following acute right ventricular pressure overload: an experimental study].

Relationships between biventricular pressures, left ventricular shape and paradoxical septal motion in patients with right ventricular pressure overload (RVPO) are unknown. To clarify these relationships, we measured left and right ventricular short-axis dimensions and ventricular pressures using anesthetized open-chest dogs with pulmonary embolizations. With repeated microembolization, right ventricular systolic pressure (RVSP) increased stepwise from a level of 27 mmHg to the maximum value of 72 mmHg. This elevation caused gradual leftward shift of the interventricular septum (IVS) both at end-diastole and end-systole. Further embolization caused collapse (shock: left ventricular systolic pressure: LVSP < 70 mmHg) with a fall in RVSP. In the state of shock, the rise in right ventricular end-diastolic pressure (RVEDP) and fall in left ventricular end-diastolic pressure (LVEDP) were prominent, and the degree of shift of the IVS became significantly greater at end-diastole than at end-systole, resulting in paradoxical motion of the IVS. There were significant linear relationships between the degree of end-diastolic IVS displacement and end-diastolic transseptal pressure (LVEDP-RVEDP), and between the degree of end-systolic IVS displacement and end-systolic transseptal pressure (LVESP-RVESP) throughout the course of repeated pulmonary microembolization even in the state of shock. In conclusion, abnormal movements of the IVS in RVPO patients indicate the presence of a marked decrease in end-diastolic transseptal pressure due to right ventricular failure.

Measurement of biventricular septal-to-free wall diameters using sonomicrocrystals.

An ultrasonic system for the measurement of biventricular septal-to-free wall internal diameters in the dog was described. The ventricular endocardial ultrasonic microcrystals were implanted via the left and right atrial appendages and arranged in a straight line, with minimal invasion of the myocardium and pericardium. Reliable signals were obtained during right ventricular pressure overload and septal myocardial ischemia.

[Effects of beta-antagonists and beta 1-partial agonists on the pulmonary pressor response to 5-HT].

The effects of beta-antagonists (propranolol, pindolol, atenolol) and beta 1-partial agonists (xamoterol, denopamine) on the pulmonary circulation, and on the pressor response to 5-HT were investigated and compared with those of a beta-agonist, isoproterenol. These agents (at doses of 0.002-20 mg) were administrated into the isolated lung lobe perfusion system excised from mongrel dogs (7-12 kg in weight). Under standard conditions (mean pulmonary inflow pressure, 15 mmHg; mean outflow pressure, 5 mmHg), propranolol and atenolol had no effect on pulmonary vascular resistance (PVR) at the tested doses, but pindolol which has intrinsic sympathomimetic activity (ISA) and two beta 1-partial agonists significantly decreased PVR in a dose-dependent manner (each n = 7). Isoproterenol, up to a dose of 0.2 mg, markedly decreased PVR, but induced vasoconstriction in larger doses (n = 7). Propranolol and xamoterol similarly reduced the pressor response to 30 micrograms of 5-HT from a dose of 2 mg, and these inhibitory actions were greater than those of the other drugs. Pindolol and denopamine inhibited the 5-HT response in a dose of 20 mg, whereas atenolol only augmented the response in a dose-dependent manner. In conclusion, beta-antagonists with ISA (including beta 1-partial agonist activity) can dilate the pulmonary vessels in a dose-dependent manner, but not beta-antagonists without ISA. Furthermore, the 5-HT inhibitory effects caused by relatively large doses of beta-antagonists, except for atenolol, may be related to the 5-HT receptor blockade or other unknown mechanisms, including calcium influx or prostaglandin synthesis, but not to the beta-receptor blockade.

Functional and geometrical interference and interdependency between the right and left ventricle in cor pulmonale: an experimental study on simultaneous measurement of biventricular geometry of acute right ventricular pressure overload.

To clarify the effects of right ventricular (RV) pressure overload on functional and geometrical interference and interdependency between the right and left ventricle, both ventricular internal diameters were measured by the microcrystal technique during lycopodium induced pulmonary embolization in the dog. By repeated embolization, RV systolic pressure was increased progressively until it reached a peak value of about 60-70 mmHg, then it began to fall. At the same time, the hemodynamics deteriorated progressively resulting in death. During the experiment, gradual leftward displacement of the interventricular septum (IVS) without any change in left ventricular (LV) free wall geometry was observed. In pulmonary embolic shock, which showed a fall in LV pressure to about 60 mmHg and cardiac output to about 40% of control, the leftward displacement of IVS became marked, and the cooperative movement of IVS to LV contraction disappeared. The IVS position during acute RV pressure overload was able to account for the transseptal pressure gradient. The importance of IVS position and motion in cardiac function during acute RV pressure overload was stressed. Furthermore, to establish the theoretical treatment in acute cardiopulmonary resuscitation, ligation of the descending aorta (AoL) or norepinephrine ("N") or isoproterenol ("I") administration were examined in a canine pulmonary embolic shock model. AoL or "N" improved the deteriorated hemodynamics with restoration of biventricular geometry. However, "I" did not restore the biventricular geometry despite the transiently improved hemodynamics, and the experimental animals were unable to survive. These results suggest the importance of the maintainance of systemic pressure for the restoration of failed RV function. Further integrated studies are required to understand biventricular interference and interdependency.