Kiminari Kobayashi

Effects of Nicorandil on Coronary Hemodynamics in Ischemic Heart Disease: Comparison with Nitroglycerin, Nifedipine, and Propranolol

Effects of nicorandil (NC), a newly synthesized nicotinamide derivative (2 mg i.v.), nitroglycerin (TNG, 0.3 mg sublingual), nifedipine (NF, 10 mg sublingual), and propranolol (PR, 0.1 mg/kg i.v.) on coronary hemodynamics were evaluated in 41 patients with ischemic heart disease. Coronary sinus flow (CSF) was measured using a continuous thermodilution method. NC decreased arterial pressure, cardiac output (CO), and pulmonary artery pressure without changing heart rate. Rate-pressure product tended to decrease. Resting CSF was increased by NC (117–148 ml/min, p < 0.01) and NF. TNG and PR caused no significant changes. Furthermore, NC revealed the highest CSF/CO ratio among four agents and decreased coronary resistance. During rapid atrial pacing, CSF was slightly increased by TNG, but remained unchanged after NC and NF. Myocardial norepinephrine release was markedly increased by TNG (1.5–6.2 ng/min, p < 0.01) and slightly increased by NF. No changes were noted after NC and PR. Myocardial lactate extraction varied insignificantly in all agents. NC is a potent coronary vasodilator and seems to reduce both preload and afterload; however, in contrast to TNG and NF, NC did not cause reflex tachycardia or an increase of myocardial sympathetic tone.

Acute Changes in Left Atrial and Left Ventricular Diameters After Physiological Pacing

The present study examined alterations in left atria! diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 ± 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters ware expressed per body surface area (LADI and LVDdl; mm/m). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 ± 0.9 L/min to 3.9 ± 1.0 L/min: P < 0.001). LADI decreased from 24.9 ± 4.2 mm/m2 to 21.8 ± 4.4 mm/m2 (P < 0.001) in 22 patients with AV block and from 24.1 ± 3.4 mm/m2 to 20.4 ± 3.8 mm/m2 (P < 0.001) in 15 SSS patients. However, LVDdl did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e. LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prim‐ to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.

The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure.

The effect of captopril on steady-state pharmacokineties of digoxin was studied in 12 patients with mild congestive heart failure (CHI New York Heart Association functional class 1 or 2). Serum and urine digoxin concentrations were determined before and after a repeated administration of captopril in the patients on chronic digoxin therapy. The patients were taking digoxin, 0.25–0.375mg day, once daily, and were concurrently administered captopril, 37.5 mg day, three times daily, for seven days. Peak serum concentration of digoxin (SCD) before and after captopril was 2.1 ± 0.2. mean ± SEM, and 2.0 ± 0.1 ng ml: the time to peak was 1.1 ± 0.2 and 1.8 ± 0.3h: the terminal half-life was 10.9 ± 1.0 and 8. ± 0.9 h. and the urea under the concentration-time curve to 24 h was 26.9 2.4 and 27.6 ± 2.11 ng h ml. There was no significant difference between patients without and with captopril in SCD and its pharmacokinetie parameters. Renal digoxin clearance and creatinine clearance also showed no significant difference. After an administration of captopril, angiotensin converting-enzyme (ACE) activity was well suppressed. These results suggest that captopril does not increase SCD in patients with CHF, and effectively suppresses ACE activity. Thus, modification in the dosage regimen of digoxin may be unnecessary in the case of coadministration with captopril.

Human Atrial Natriuretic Peptide in Aortic and Coronary Sinus Blood During Atrial Pacing in Patients with Ischemic Heart Disease

Summary: This study investigated the plasma concentrations of human atrial natriuretic peptide (hANP) of blood samples obtained from the aorta and coronary sinus (CS) in 19 male patients (mean age of 52.8 ± 2.1 years) with ischemic heart disease before and during atrial pacing. The plasma concentrations of hANP were measured by radioimmunoassay, and the secretion rate of hANP was calculated on the basis of the CS-aorta difference in plasma hANP concentration and the CS flow rate recorded at blood sampling. Before atrial pacing, aortic plasma hANP concentration showed a significant positive correlation with mean pulmonary capillary wedge pressure (r = 0.67, p < 0.002) or mean pulmonary artery pressure (r – 0.71, p < 0.001), and a significant negative correlation with left ventricular ejection fraction (r = −0.50, p < 0.05). During atrial pacing, aortic plasma hANP concentration increased from 67 ± 13 (SEM) to 151 + 33 pg/ml (p < 0.01), CS plasma hANP concentration from 727 ± 121 to 1205 ± 228 pg/ml (p < 0.01), and the hANP secretion rate from 45.4 ± 14.8 to 86.8 ± 28.2 ng/min (p < 0.05, n = 12). The aortic plasma hANP concentration was significantly correlated with the CS plasma hANP concentration (r = 0.81. p < 0.001) or the hANP secretion rate (r = 0.70, p < 0.001). When the patients were divided into the old myocardial infarction group (n = 10) and the angina pectoris group (n = 9), the aortic plasma hANP concentration was significantly higher in the former than in the latter before pacing (p < 0.05). The change in aortic plasma hANP concentration during pacing was significantly smaller in the infarction group than in the angina group (p < 0.05). These results suggest that the secretion rate of hANP determines the circulating level of hANP at rest and during atrial pacing and that the secretion of hANP is influenced by cardiac function.