Keizo Bito

Plasma atrial natriuretic polypeptide as an index of left ventricular end-diastolic pressure in patients with chronic left-sided heart failure

To evaluate the relationship between plasma atrial natriuretic polypeptide (ANP), hemodynamic parameters, and plasma catecholamines and, in addition, to determine whether circulating ANP is metabolized in the pulmonary circulation, plasma concentrations of ANP were determined in 40 patients with chronic left-sided heart failure. After at least 30 minutes of bed rest with the patient in the supine position, blood samples were drawn simultaneously from both the main pulmonary artery (mPA) and the ascending aorta (Ao) before administration of contrast medium. The plasma ANP concentrations significantly decreased from the mPA to the Ao (135.3 +/- 18.1 pg/ml vs 127.4 +/- 19.4 pg/ml; mean +/- SEM, p less than 0.05). The plasma ANP level in the mPA correlated with the plasma norepinephrine level in the Ao (r = 0.71, p less than 0.01), right atrial pressure (r = 0.34, p less than 0.05), mean pulmonary capillary wedge pressure (r = 0.829, p less than 0.001), and left ventricular end-diastolic pressure (LVEDP) (r = 0.88, p less than 0.001). Of the various hemodynamic parameters and plasma catecholamine concentrations in the Ao, only LVEDP was found to be an independent and significant predictor of plasma ANP levels in the mPA. These results indicate that ANP released from the heart is regulated mainly by preload (LVEDP) in cases of left-sided heart failure and that circulating ANP is metabolized in the pulmonary circulation. In conclusion, the plasma ANP concentration may be a useful noninvasive index of LVEDP in patients with chronic left-sided heart failure.

Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris

Nicorandil therapy was compared with placebo therapy in 11 patients with chronic stable angina pectoris. A computer-assisted treadmill exercise test was performed after administration of either 10 or 30 mg of nicorandil. Analysis of variance showed a significant difference among placebo and nicorandil treatments (p less than 0.01). Ten milligrams of nicorandil prolonged time to onset of ischemia 36% (p less than 0.05) but increased the exercise duration only 15%. Thirty milligrams of nicorandil prolonged time to onset of ischemia 82% (p less than 0.01) and exercise duration 45% (p less than 0.01). Both time to onset of ischemia and exercise duration increased progressively from the 10-mg to the 30-mg dose (p less than 0.05). Heart rate at rest was significantly higher and systolic pressure at rest significantly lower with 30 mg of nicorandil than with placebo. After administration of 30 mg of nicorandil there was a significant reduction in ST depression associated with a slight decrease in the double product at the end of Bruce stage 2 exercise. The peak double product was greater after administration of 30 mg of nicorandil than after placebo, indicating an increased myocardial oxygen supply to the ischemic area. The plasma concentration of nicorandil averaged 78 +/- 83 ng/ml with the 10 mg and 313 +/- 142 ng/ml with 30 mg. There was an increase in exercise duration of more than 1 minute in 8 of 9 patients who had plasma nicorandil concentrations greater than 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a cardiotonic agent, TA-064, on isolated canine cerebral, coronary, femoral, mesenteric, and renal arteries.

We investigated the effects of a newly synthesized cardiotonic agent, TA-064, on helical strips of isolated canine cerebral, coronary, femoral, mesenteric, and renal arteries. TA-064 had no effect on isolated arterial strips under resting tension. When the arterial strips were partially contracted with prostaglandin F2α, TA-064 caused markedly significant concentration-related relaxations in coronary arterial strips. However, the maximum relaxation induced by TA-064 in renal, mesenteric, and femoral arterial strips was only one-third or less of the coronary artery. On the other hand, cerebral arterial strips generated negligible responses to TA-064. Relaxation of renal, mesenteric, and femoral arteries was not potentiated by pretreatment with 10−5 M phenoxybenzamine. The concentration-response curve for TA-064 in coronary artery was shifted to the right to a similar extent by exposure to 2 × 10−7 M propranolol and 2 × 10−7 M metoprolol. On the other hand, relaxation of renal arterial strips was only slightly attenuated by metoprolol but was inhibited by propranolol. Droperidol (3 × 10−5 M) failed to significantly alter the concentration-response curve for TA-064 in coronary artery. These results indicate that TA-064 causes coronary arterial vasodilatation mediated by β1-adrenoceptors. It would further appear that the same mechanism may be responsible for the positive inotropic action of TA-064.