Differing effects of liraglutide on gastric emptying in Japanese patients with type 2 diabetes.

This study was performed to clarify the influence of liraglutide on gastric emptying in Japanese patients with type 2 diabetes. In 16 patients, the [(13) C]-acetate breath test was performed to compare gastric emptying before and after liraglutide treatment. We found two patterns of response, with gastric emptying being delayed by liraglutide in seven patients (delayers) and not delayed in nine patients (non-delayers). The mean increase of the maximum gastric emptying time was 31 ± 4 min (p < 0.01 vs. baseline) in the delayers, while it was only 2 ± 3 min (p = 0.60 vs. baseline) in the non-delayers. The delayers showed a greater early decrease of AUC-PG from 0 to 60 min, despite no increase of the plasma insulin level compared with non-delayers. In conclusion, the effect of liraglutide treatment on gastric emptying shows heterogeneity, and patients can be classified as delayers or non-delayers.

Haemodynamic effects of new beta-blockers with vasodilatory properties in essential hypertension.

Six weeks of treatment with carvedilol, N-696, celiprolol, dilevalol, acebutolol, urapidil, doxazosin and altiopril reduced blood pressure with various changes in heart rate. Cardiac index decreased and total peripheral resistance index (TPRI) stayed at the pretreatment levels in the carvedilol, N-696 and acebutolol groups, whereas TPRI tended to decrease in the celiprolol (p less than 0.05), dilevalol (p less than 0.05), urapidil, doxazosin (p less than 0.05) and altiopril groups; cardiac index was unchanged in these groups. As carvedilol and N-696 have no beta 1-selectivity and no intrinsic sympathomimetic activity (ISA), their direct vasodilating property (and the possible alpha-blocking activity of carvedilol) may precipitate in minimising an increase in TPRI induced by vascular beta 2-blockade and suppressed cardiac pump function. Celiprolol and dilevalol, with beta 2-selective ISA, reduced cardiac index slightly and insignificantly, and decreased TPRI. These results indicate that ISA on vascular beta 2-receptors may induce vasodilatation and ISA on cardiac beta 2-receptors may counteract cardiac beta 2-blockade. Differences in haemodynamic responses between these drugs with ISA and vasodilators such as alpha-blocking agents (urapidil and doxazosin) and an ACE inhibitor, altiopril, may be attributable to manifestation of cardiac beta-blockade as observed in the drugs with ISA.

Changes of heart rate and QT interval at high altitude in alpinists: analysis by Holter ambulatory electrocardiogram.

The purpose of this study is to record continuously electrocardiograms of alpinists during different activities practiced in mountaineering, compare heart rate and QT interval at high altitude with those at sea level, and compare alpinists with nonalpinists. Analysis was attempted on 14 alpinists (9 male, 5 female, ages 26-45) to determine changes in heart rate and QT interval using continuous ambulatory electrocardiograms recorded at sea level and high altitude. Between 1983 and 1984, 9 of 14 alpinists (6 male, 3 female) were subjected to the study at high altitude, that is, at Mt. Kangchenjunga (Himalaya), Mt. Satopanth (Himalaya), and Mt. Jitudake (Butan), 4400 to 7800 m (mean 5710 m). The following were noted: Heart rate at high altitude was significantly higher both in daytime and nighttime. The circadian rhythm of the heart rate disappeared at extremely high altitude in several alpinists. A high correlation was noted between measured QT interval (QTm) and RR interval (r = 0.81, p = 0.005). Nighttime QTm at high altitude was prolonged in comparison with that of daytime so far as the RR interval remained the same. At high altitude, the nighttime corrected QT interval (QTc) was also significantly prolonged in spite of shortened RR interval. The mechanism of QTc prolongation is not clear. Many factors may impact on the QT interval during mountaineering.

Effect of pindolol and nifedipine alone and in combination on haemodynamic parameters/variables in essential hypertension.

Thirteen patients with essential hypertension were started on pindolol 10-20 mg daily and twelve on nifedipine 20-60 mg daily. At the end of 6 weeks inadequate responders (B.P. greater than 140/90) were put onto combined treatment with both drugs, ten of the pindolol and six of the nifedipine patients being affected. Combined therapy then continued for a further 6-week period, while adequate responders (B.P. less than 140/90) continued with their initial drug. In addition to blood pressure, heart rate and cardiac index were also measured, and total peripheral resistance index was calculated. Where blood pressure decreased below 140/90 at the end of 12 weeks in patients on combined treatment, the original drug was withdrawn, leaving the patient on a single-drug regimen again, this time with the 'second compound'. This manoeuvre was followed by a rise in blood pressure in five out of eight patients in whom pindolol was withdrawn and in two out of six after nifedipine withdrawal. No definite conclusions can be drawn from these findings, and it may be that a better approach to the problem of poor responders would be to try each drug on its own before combining them, rather than combining first and then withdrawing the initial treatment. The increased peripheral resistance typical of essential hypertension was not adversely affected by either drug, while combined treatment had a beneficial effect on this parameter.

Possible significance of the pharmacological differentiation of beta-blocking agents in hemodynamic effects in essential hypertension.

Thirteen beta-blocking agents with different pharmacological properties were administered orally to 161 outpatients with essential hypertension for 5 weeks to assess their hemodynamic effects. Cardioselective ones, such as atenolol, metoprolol and acebutolol, reduced mean blood pressure (MBP) and the cardiac index. (CI) without any changes of the total peripheral resistance index. (TPRI). In the total 44 patients treated with these drugs, a positive correlation (r = 0.529, p less than 0.005) was found between the decrease in MBP and that of TPRI, but the decrease in MBP did not correlate with that of CI. Effects of non-cardioselective ones were classified arbitrarily into the following 3 patterns: 1) reduction of CI of more than 0.50 L/min/m2 and a slight increase of TPRI by more than 150 dyne . sec . cm-5 . m2 (nadolol, propranolol, o.prenolol and penbutolol), 2) reduction of TPRI by more than 150 dyne . sec . cm-5 . m2 (pindolol, bunitrolol and labetalol) and 3) the intermediate hemodynamic responses between the two patterns described above (carteolol, bupranolol and bufetolol). In all these 3 groups, the decrease in MBP correlated with that of TPRI (the first group, n = 45, r = 0.557, p less than 0.005; the second, n = 37, r = 0.525, p less than 0.005; the third, n = 35, r = 0.612, p less than 0.005), but did not correlate with the decrease of CI. These results suggest that the antihypertensive effects of beta-blocking agents mainly depend on the reduction of peripheral resistance, although their pharmacological properties are not uniform and their cardiodepressant effects are variable. Reduction of cardiac performance with these beta-blocking agents seemed to be a consequence of overall pharmacological actions including beta-receptor blockade, central effects and membrane stabilizing effects, and it may be antagonized by intrinsic sympathomimetic activity and the reduction in afterload for the heart. Vascular beta-receptor blocking action may play a part in decreasing the degree of reduction of the total peripheral resistance index, while their intrinsic sympathomimetic action on the vascular site may induce vasodilating effects.

Hemodynamic effects of beta-adrenergic blockade with pindolol, oxprenolol, propranolol and bufetolol hydrochloride in essential hypertension.

Hemodynamic studies (using (131)I-labeled albumin [RISA]) Were performed before and 5 and 42 weeks after the oral administration of pindolol (av. 30 mg/day), oxprenolol (av. 216 mg/day), propranolol (av. 75 mg/day) or bufetolol hydrochloride (av. 30 mg/day) in 40 patients with essential hypertension. Responders to the antihypertensive actions of short-term (5 weeks) pindolol or bufetolol showed a reduction in total peripheral resistance (pindolol, from av. 2622 to 2022 dyne-sec-cm-5-m2; befetolol, from av. 3301 to 2620, p less than 0.05), without significant changes in cardiac index, while hypotensive actions of propranolol or oxprenolol appeared to be due mainly to a decrease in cardiac output (propranolol, from av. 4.03 to 2.99 L/min/m2; oxprenolol, from av. 3.97 to 3.29 L/min/m2), although the decrease in cardiac output was not significant. In long-term (42 weeks) oxprenolol therapy, antihypertensive effects seemed to be related to reduced cardiac output and a readaptation of peripheral resistance to chronic reduction of cardiac output was not always observed. Circulation time was determined in 9 patients with oxprenolol therapy and 8 with pindolol therapy by the measurement of the arrival time in the cerebral hemisphere of the intravenously injected radioisotope. The patients with oxprenolol therapy showed significant prolongation in circulation time (short-term administration, av. 6.6 to 8.4 sec; long-term administration av. 6.6 to 9.2 sec, p less than 0.05), while no prolongation was observed in pindolol therapy. These results suggest that hemodynamic responses to beta-blocking agents are not uniform and that the antihypertensive actions of beta-blockers depend on the effects on both cardiac output and peripheral vascular resistance.