Yoshihiko Ojiri

Uneven Changes In Circulating Blood Cell Counts With Adrenergic Stimulation To The Canine Spleen

1. Responses of splenic diameter measured by sonomicrometry to α‐ and β‐adrenoceptor stimulants were estimated together with simultaneously measured systemic arterial and splenic venous concentrations of red blood cells (RBC), white blood cells (WBC) and platelets (PLT) in anaesthetized dogs.

Haemodynamic and haematologic effects of Acanthaster planci venom in dogs

This study was designed to examine haemodynamic and haematologic effects of the crown-of-thorns starfish venom (Acanthaster planci venom: APV) in dogs. Severe systemic hypotension, thrombocytopenia and leukopenia were induced by APV (1.0 mg protein/kg i.v.), followed by gradual return to the baseline level within 60 min. Hypotension was presumably caused by two factors: an early decrease in systemic vascular resistance and the large reduction in cardiac output due to reduced ventricular filling. Indomethacin, a cyclooxygenase inhibitor, remarkably suppressed systemic hypotension induced by APV. The peak reduction in systemic pressure was associated with concomitant rise of plasma 6-keto-PGF1 alpha, a major stable metabolite of prostacyclin. Thus, the hypotensive effect of APV may be caused primarily by prostacyclin and/or some vasodilating prostaglandins. In contrast, thrombocytopenia and leukopenia were not affected by cyclooxygenase inhibitor, 5-lipoxygenase inhibitor or platelet activating factor (PAF) receptor antagonist. When APV was administered repeatedly, tachyphylaxis was developed in haemodynamic effects, but not in haematologic effects. These findings suggest that APV-induced hypotensive effects may occur mainly through endogenous production of vasodilating prostaglandins including prostacyclin, although APV-induced thrombocytopenia and leukopenia may be caused by other mechanism(s) unrelated to arachidonate metabolites and/or PAF.

Involvement of nitric oxide and eicosanoids in platelet-activating factor-induced haemodynamic and haematological effects in dogs

1 Platelet‐activating factor (PAF) is a phospholipid mediator with potent cardiovascular and haematological actions. But its mechanisms of action in vivo have not been fully elucidated, probably due to difficulties arising from previous findings that the effects of PAF are largely mediated by the release of a variety of other autacoids. In the present study, the roles of nitric oxide and eicosanoids in the effects of PAF (0.01‐0.25 μg kg−1 i.v.) on systemic and pulmonary vasculatures and circulating blood cell count were pharmacologically evaluated in anaesthetized dogs. 2 Higher doses of PAF (>0.1 μg kg−1) produced a biphasic systemic hypotension. The first hypotension seen 30 s after the injection was accompanied by a decrease in systemic vascular resistance, thrombocytopenia and leukopenia, while the second hypotension seen 1–2 min after PAF was accompanied by a marked rise in pulmonary vascular resistance and decreases in aortic blood flow and cardiac contractility. Lower doses of PAF (0.01‐0.05 μg kg−1) caused only the first responses in a dose‐dependent manner. 3 Pretreatment with indomethacin inhibited the second responses to PAF without affecting the first responses. The thromboxane A2/prostaglandin H2 (TP)‐receptor antagonist vapiprost blocked the PAF‐induced rise in pulmonary vascular resistance. AA‐861, a 5‐lipoxygenase inhibitor, attenuated the PAF‐induced cardiac depression. The nitric oxide synthase inhibitor NG‐nitro‐l‐arginine methyl ester inhibited the PAF‐induced early decrease in systemic vascular resistance. 4 All observed changes in haemodynamics and blood cell count after PAF were almost abolished by TCV‐309, a PAF‐receptor antagonist. 5 Reproducible hypotension and thrombocytopenia produced by a lower dose of PAF (0.05 μg kg−1) were respectively attenuated and potentiated by pretreatment with NG‐nitro‐l‐arginine, another nitric oxide synthase inhibitor. Administration of l‐arginine reversed the effects of the nitric oxide synthase inhibitor. 6 These results indicate that PAF‐receptor‐mediated production of not only eicosanoids but also nitric oxide may contribute to the cardiovascular and haematological responses to PAF in the dog.

Cardiovascular Effect of a Senso (Toad Venom)-Containing Drug in Anesthetized Dogs (2): Influence of Propranolol

Effects of a Senso (toad venom)-containing drug KY on systemic hemodynamics were examined, and participation of beta-adrenoceptor in its action was evaluated by using propranolol in anesthetized dogs. KY produced a positive inotropic action, and decreased total peripheral (TPR) and coronary vascular resistances (CR), while renal vascular resistance (RR) was increased. After propranolol, KY significantly increased TPR, CR, vertebral vascular resistance and RR. KY-induced positive inotropic action was partly diminished but not abolished by beta-blockade. These results indicate that the beta-adrenergic action may be involved in the vasodilating effect of KY and partly in the positive inotropic action.

Effects of a senso (toad venom) containing drug on systemic hemodynamics, cardiac function and myocardial oxygen consumption in anesthetized dogs

Effects of a Senso (toad venom)-containing drug, KY, on cardiovascular system were examined in anesthetized open-chest dogs. KY increased aortic pressure, peak positive first derivative of left ventricular pressure, stroke work index, percent segment shortening in left ventricular myocardium and myocardial oxygen consumption, and decreased heart rate and total peripheral vascular resistance (TPR). Propranolol augmented the increase in aortic pressure with KY, inhibited the increase in aortic flow with KY and reversed KY-induced decrease in TPR to an increase. These results indicate that KY has positive inotropic and vasodilating actions possibly originating from both digitalis- and adrenaline-like action of a Senso.

Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: Comparison with nitroglycerin and cromakalim

Summary— Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous iv infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end‐diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered iv after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with iv NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

Alleviation of myocardial dysfunction and abnormal lactate metabolism during coronary stenosis in dogs by ICI 118,551

Hemodynamic parameters, segment shortening in the ischemic myocardium and cardiac lactate extraction were estimated in the presence of a critical coronary stenosis, before and after administration of the selective beta 2-adrenoceptor antagonist, ICI 118,551, or the beta 1-adrenoceptor antagonist, atenolol, to anesthetized dogs. ICI 118,551 (0.2 and 0.5 mg/kg i.v.) and atenolol (0.2 mg/kg i.v.) produced significant decreases in both heart rate (by 6, 14 and 20% of the predrug value, respectively) and maxLVdP/dt (by 15, 26 and 24% of the predrug value, respectively). ICI 118,551 (0.5 mg/kg) and atenolol significantly improved the impaired shortening of the myocardial segment when compared with the change seen after saline administration. ICI 118,551 at both doses and atenolol significantly increased depressed cardiac lactate extraction while saline did not. Increasing heart rate by pacing abolished the beneficial effects of ICI 118,551 and atenolol on ischemic myocardial segment shortening and lactate metabolism. The data suggest that not only beta 1- but also beta 2-adrenoceptor blockade may contribute to the amelioration of myocardial ischemia in a model of coronary stenosis.