The hemodynamic effects of milrinone (Mil) were studied in 11 patients with congestive heart failure (CHF) and New York Heart Association (NYHA) functional class II-IV before and after a 2-week treatment. The plasma concentration of Mil was also determined and its pharmacokinetics analyzed. The effect of a placebo was examined before the initiation of the treatment. At the onset, the hemodynamic effects of a single oral dose of Mil (7.5 mg) were evaluated. Mil increased the cardiac index significantly (p<0.05) 4 h after administrations from 2.3±0.4 to 2.9±0.6 L/min/m². The pulmonary capillary wedge pressure (PCW) was lowered significantly by Mil (p<0.05) between 0.5 and 4 h after administration. After a 2-week treatment, the baseline PCW dropped (p<0.05) and the NYHA functional class improved in 10 patients. One patient remained in the same class (II). The improved NYHA class was maintained in 6 patients tested after a mean interval of 163 months. Single oral administration of Mil (7.5 mg) induced hemodynamic improvements after 2-week treatment and the drug also induced similar improvements even after the chronic oral therapy with Mil for 16±3 months. Pharmacokinetic analysis showed a significant increase in the area under the curve after 2 weeks of treatment. We conclude that Mil decreases the PCW and probably increases the cardiac index and thus improves the symptoms and NYHA functional class in patients with CHF.

View full abstract

The exponential correction of the QT interval (eQTc) was studied using 12, 543 resting electrocardiograms obtained in children (first and seventh graders) who were screened for heart disease in Kagoshima City. The values of eQTc to minimize the effect of the RR interval were estimated using following exponential model, eQTc=(QT interval)/(RR interval)^k. The parameter k=0.31 was found to be the most useful exponent. The distribution of eQTc values showed a hiatus or break at probability points near p<0.001 or p<0.0005. Tentative criteria for an abnormally long eQTc Were selected using these points and the following convenient data: 0.430 and 0.435 for the male and female first graders, and 0.440 and 0.445 for the male and female seventh graders, increased by 0.005, respectively. Abnormal values must ultimately be selected using data on patients with the long QT syndrome; however, our findings suggest that the exponential correction of the QT interval may be useful in large-scale screening programs for detecting a QT prolongation in young school children.

View full abstract

We studied the rotation angles on the each of 3 axes and the planarity and roundness of QRS loop when its plane was laid close to horizontal in 4 groups of patients. Thirty five had anterior myocardial infarction, 34 inferior infarction, 15 non Q wave inferior infarction, and 34 were normal subjects. The rotation angles of the QRS loop were significantly different from the controls, on the Y and Z axes in the anterior infarction group, on the Z axis in the inferior infarction group and on the X axis in the non Q wave inferior infarction group (p<0.01). The planarity index in the inferior infarction group was significantly higher (p<0.01) than in other groups. The significantly smallest value of the roundness index was noted in the anterior infarction group (p < 0.01). Significant features of the early segmental planarity indexes were shown in the non Q and Q wave inferior infarction groups (p<0.01). We conclude that the rotation angles and the planarity and roundness indexes are characteristic parameters for the infarct group and may be useful for diagnosing myocardial infarction, which is difficult with electrocardiography and vectorcardiography.

View full abstract

To determine the factors influencing the spontaneous remission of variant angina, clinical characteristics were examined in 75 Japanese patients with variant angina. Spontaneous remission was defined as an absence of angina at rest for at least 3 months after withdrawal of treatment with calcium antagonists. This remission occurred in 12 patients (16%) (remission group), while angina persisted despite treatment with calcium antagonists and nitrates in 33 patients (44%) (persistent angina group). The remaining 30 patients (40%) were angina-free under treatment with calcium antagonists and/or nitrates (angina-free on treatment group). The prevalence of significant coronary artery stenosis (>75%) was significantly higher in the remission group than in the persistent angina group (44% vs 7%, p<0.05). The prevalence of cessation of smoking was significantly higher in the remission group than in the persistent angina group (92% vs 39%, p<0.01). Age, gender, other coronary risk factors, disease activity of variant angina and site of myocardial ischemia during anginal attacks were not statistically different among the 3 groups. There data indicate that remission of variant angina occurs more frequently in patients with than in those without significant coronary artery stenosis and that cessation of smoking is an important factor for remission of variant angina.

View full abstract

Electrocardiographic criteria for right ventricular (RV) hypertrophy in infants generally exhibit low sensitivity in terms of diagnostic accuracy. We studied the QRST isointegral map (QRST-Imap) of body surface potential distribution for the diagnosis of RV overload in patients less than 2 years old. Patients with atrial septal defect (ASD), pulmonary stenosis (PS) and tetralogy of Fallot (TOF) were examined (RV overload group) and the findings of their QRST-Imaps were compared to those of age-matched healthy infants (NOR). QRST-Imaps in RV overload showed abnormal findings, with two maxima or a rightward shift of the maximum with increased amplitude, in contrast to one maximum at the left anterior chest with a single dipole pattern in the NOR group. ASD patients had two maxima with a decreased integral value between them. In PS, two maxima were also observed, with increased integral values of the right maximum as the RV systolic pressure was elevated. TOF patients showed a single maximum shifted to the anterior median line with increased amplitude. These results indicate that the findings of QRST-Imaps are of value in detecting the presence and pattern of RV overload in infants.

View full abstract

We investigated the effects of recombinant human erythropoietin (rHuEPO) therapy on exercise capacity by symptom-limited maximal treadmill exercise testing in 9 patients with coronary artery disease who were receiving maintenance hemodialysis. The initial hemoglobin concentration of 7.9±0.7g/dl, (mean±S.D.) rose to 10.4±1.1 g/dl, (p<0.01) after three months of rHuEPO therapy. The partial correction of renal anemia resulted in a significant increase in exercise duration (from 278±84 sec to 384±74 sec, p<0.01) and maximum pressure-rate product (from 228.3±50.3mmHg·bpm/l0² to 262.8±40.4 mmHg·bpm/10², p<0.01). The maximum exercise-induced ST segment depression significantly decreased after treatment (from 1.3 ±0.5 mm to 0.5±0.5 mm, p<0.05). These results suggest that the improvement in maximum coronary oxygen supply exceeded the increased maximum myocardial oxygen requirements after the partial correction of renal anemia by rHuEPO therapy in hemodialysis patients with coronary artery disease.

View full abstract

Iodine-labelled fatty acids have been proposed as new tracers of cardiac metabolisms. However, it is not clear how these tracers would reflect the intracellular metabolism. Therefore, we measured the uptake and release of iodine 125-labelled phenylpentadecanoic acid (IPPA), its β-methyl substitute (BMIPP) and ²⁰¹Tl in cultured myocytes of mouse embryos, and compared these values to intracellular adenosine triphosphate (ATP) content after metabolic inhibitions of oxidative phosphorylation by sodium cyanide (CN), glycolysis by 2-deoxyglucose (2-DG) or fatty acid β-oxidation by lactate. The uptake and release of BMIPP was not changed by any inhibitors suggesting BMIPP would not be metabolized in the myocytes. The uptake of IPPA was significantly reduced by 2DG and 60-80% of IPPA was metabolized to hydrophilic catabolites. The correlation of BMIPP and IPPA uptake to intracellular ATP content were high (r=0.89, p<0.05; r=0.86, p<0.1), but there was poor correlation of ²⁰¹Tl to ATP values (r=0.53, n.s.). These results suggested that iodine-labelled fatty acids could be used as better tracers of myocardial metabolism than ²⁰¹Tl.

View full abstract

Effects of reduction of blood pressure and regression of left ventricular hypertrophy following hydralazine and captopril therapy on ischemic cardiac function and myocardial metabolism were studied in spontaneously hypertensive rats (SHR). Hydralazine (1.5 or 3 mg/kg/day) and captopril (50 or 100 mg/kg/day) were administered to SHR from 19 to 26 weeks of age. Both hydralazine and captopril significantly decreased arterial blood pressure in SHR, but only captopril significantly reduced left ventricular weight. The percentage of V₃ myosin isozyme significantly decreased in captopril-treated SHR compared to hydralazine-treated SHR. At the end of long-term treatment, hearts were removed and perfused for 15 min by the working heart technique, and then global ischemia was induced for 30 min. The ischemic heart was reperfused for 30 min. In hydralazine-treated SHR and captopril-treated SHR, the pressure-rate product and extent of recovery of the coronary flow during reperfusion following 30 min of ischemia were higher than those in control SHR, but this difference was significant only in captopril-treated SHR. Hydralazine and captopril treatment improved the restoration of the levels of ATP, creatine phosphate, total adenine nucleotide and energy charge potential in SHR after reperfusion following 30 min of ischemia, but only captopril had a significant effect. In conclusion, regression of left ventricular hypertrophy is more important than lowering of blood pressure in order to improve the ischemic myocardial damage.

View full abstract

To determine whether or not leukotrienes are associated with pulmonary edema after coronary ligation in dogs, we studied the effects of a specific leukotriene C4/D4 antagonist, ONO-1078, on extravascular lung water, as measured by the thermal-dye double indicator dilution method (Extravascular thermal volume, ETV). Six dogs served as a sham control (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in 6 dogs (group 2), and in 6 others the coronary artery was ligated after pretreatment with ONO-1078 (1μ/kg/min) (group 3). ETV and pulmonary arterial pressure were measured at control and 45 min after coronary ligation. In group 1, no significant change was found in ETV. Although there was no significant increase in pulmonary arterial pressure after coronary ligation, ETV significantly increased in groups 2 and 3. ETV increased more in groups 2 and 3 than in group 1, but there was no significant difference between groups 2 and 3. Thus, ONO-1078 did not effectively prevent the accumulation of extravascular lung water after coronary ligation, indicating that leukotrienes are not important mediators of pulmonary edema after myocardial ischemia.

View full abstract