Fumio Takenaka

Activation of afferent cardiac sympathetic nerve fibers of the cat by pain producing substances and by noxious heat

SummaryAfferent discharges of 64 single units were recorded from the left cardiac sympathetic nerve of anesthetized cats. Mechano-sensitive terminals of the afferent fibers were localized in the extrapulmonary part of the pulmonary artery, left atrium, left ventricle and left pericardium, as determined by direct mechanical probing of the heart after death of the animals. Conduction velocity of the fibers ranged from 2.5 to 14.6 m/s. Excitation of these Aδ-fibers with mechanically excitable endings was produced by intravenous injections of acetylcholine, 5-hydroxytryptamine, bradykinin, histamine and veratridine, and/or by topical application of these agents to the receptor region. Noxious heat to the mechanically excitable field in the wall of the pulmonary artery and the left ventricle also activated their afferent fibers. These observations provide evidence for a certain number of afferent units in the cardiac sympathetic nerve with polymodal sensitivity. These afferent fibers can provide the spinal cord with information not only on mechanical changes in cardiac events, but also changes in the chemical environment of the cardiac nerve ending, possibly produced by myocardial ischemia.

High-energy phosphate contents of subepicardium and subendocardium in the rat treated with isoproterenol and some other drugs

Abstract High-energy phosphate content of the myocardium was reduced after subcutaneous injection of isoproterenol in rats. ATP was significantly decreased 24 h after the administration of isoproterenol 0.25 mg/kg, while creatine phosphate (CP) remained unchanged until the doses more than 1 mg/kg were used. In doses higher than 2.5 mg/kg, CP as well as ATP was markedly declined, becoming 50% of the control at 25 mg/kg. Pretreatment with propranolol prevented the reduction of high-energy phosphate content by isoproterenol. In rat hearts without isoproterenol, the content of inorganic phosphate (Pi) and lactate was significantly higher in subendocardium than in subepicardium, while CP was significantly lower in subendocardium and there was no appreciable difference in ATP. In isoproterenol-treated hearts, the difference of the phosphate content became much more prominent. When used in rats without isoproterenol, propranolol tended to increase high-energy phosphate content in subendocardium, and the difference of Pi and CP between the two layers became significantly smaller. Itramin tosylate rather decreased the CP content in subendocardium and the difference became more marked. Phenylephrine did not produce any change in the phosphate content of the two layers. It was considered that besides a relative myocardial hypoxia, characteristic exhaustion of high-energy phosphate compounds due to betareceptor stimulation may be involved in the isoproterenol-induced disturbances in rat myocardial metabolism. The physiologically existing anaerobic metabolism in subendocardium seemed to be difficult to improve with drugs affecting coronary hemodynamics. The effectiveness of propranolol may be based on the reduction in heart rate and contractility resulting from beta-receptor blockade.

Effects of isoproterenol on myocardial lipid metabolism in rat hearts perfused with and without exogenous substrates

Abstract Effects of isoproterenol on myocardial lipid metabolism were studied in perfused rat hearts by the Langendorff apparatus without recirculation. Fatty acids in phospholipid, free fatty acid and partial glyceride fractions did not alter during the initial 30-min perfusion. However, fatty acids in triglyceride fraction decreased along with the perfusion. Isoproterenol enhanced the decrease in triglyceride fatty acid in the presence of glucose, but not in the absence of glucose. When hearts were perfused for 30 min with exogenous myristirate in the presence of glucose, triglyceride fatty acid did not decrease in the control perfusion, and incorporation of myristiric acid into triglyceride fraction increased in the presence of isoproterenol. When hearts were perfused with myristirate in the absence of glucose, fatty acid in triglyceride fraction slightly decreased during the control 30-min perfusion, and marked bradycardia or ventricular arrest occurred within 10 min after the start of perfusion with solution containing isoproterenol. Triglyceride content 10 min after perfusion was not different from the control value. Mechanical performance of hearts with myristirate and isoproterenol improved when the amount of glucose in the perfusing solution was increased. The findings indicate that glucose may play an important role in the mechanical performance of the heart perfused with a solution containing isoproterenol.

An increase of cathepsin D activity in cardiac lymph and pericardial fluid induced by experimental myocardial ischemia in the dog

Abstract Cathepsin D activity was measured in the cardiac lymph, pericardial fluid and plasma after ligation of the left coronary artery of the dog. The activity of cathepsin D increased both in the cardiac lymph and the pericardial fluid after the coronary ligation, while that in the plasma did not show any increase. In sham operated group, there was practically no change in the cathepsin D activity. The increase in the cathepsin D activity in the cardiac lymph and the pericardial fluid may indicate an increase in amount of myocardial lysosomal enzymes liberated into the interstitial space during myocardial ischemia.

Effects of epinephrine and beta adrenergic blocking agents on coronary circulation and myocardial metabolism

The impl i ca t ion of the card iac s y m p a t h e t i c nerve and the role of ca techolamines have recen t ly been emphas ized in the e t io logy of angina pec tor i s (MA~KAWA 1956; RAAn 1960). As the h e a r t is a m p l y i n n e r v a t e d wi th s y m p a t h e t i c fibers the coronary c i rcula t ion mus t be exposed to the influence of s y m p a t h e t i c s t imula t ion . Since the classic expe r imen t s of LA~GW~])O~F~ a n d MORAW~TZ, the p rob lem whe the r s y m p a t h o m i m e t i c ac t ion produces const r ic t ion or d i l a t a t i on of coronary b lood vessels has been the sub jec t of considerable con t roversy (GR~GG 1950). Recen t s tudies b y HASHIMOTO et al. (1960) p rov ided evidence for the exis tence of s y m p a t h e t i c vasocons t r i c to r and p a r a s y m p a t h e t i c vasod i l a to r recep tors in the co ronary vessel wall. The p resen t s t u d y was a t t e m p t e d to re inves t iga te t he effect of ep inephr ine and to e luc ida te the mechan i sm of i ts ac t ion on coronary b lood flow, wi th special reference to myoca rd i a l oxygen, l a c t a t e and p y r u v a t e metabo l i sm. The analys is of t he p roper t ies of adrenergic receptors in co ronary c i rcula t ion was also carr ied ou t wi th use of b e t a adrenergic b locking agents , s y m p a t h e t i c denerva t ion , reserp in iza t ion , a n d coronary vascu la r s t r ip p repara t ions .

High-energy phosphate metabolism of isolated coronary arteries in the dog.

The correlation between phosphate metabolism and isometric contraction was investigated in helical strips from dog coronary artery. Adenosine triphosphate (ATP) and creatine phosphate (CP) contents of resting strips did not significantly change during anoxia. ATP content remained unchanged during potassium-contracture under aerobic conditions but was significantly reduced by anoxia. Pretreatment with iodoacetate resulted in a striking reduction in ATP content with a less marked decrease in CP content. ATP-depleting effect of iodoacetate was reduced slightly by the addition of pyruvate, but contractile response was not restored. It is considered that high-energy phosphates provided by anaerobic glycolysis can meet the energy requirements of resting coronary vessels but are insufficient for maintaining active tension. In resting strips equilibrated for 2 h in oxygenated bath solution, the reactivity to KCl and anoxia appears to be dependent on the availability of ATP.

Effects of increased cardiac mechanical performances on flow rates of cardiac lymph in dogs

SummaryRelationship between flow rates of cardiac lymph (LF), and coronary blood flow (CF), coronary perfusion pressure (PP), left ventricular peak systolic pressure (LVSP) and heart rate (HR) was studied in open-chest dogs. Intra-coronary administration of catecholamines (CA) and electrical stimulation of the cardiac sympathetic nerve (ES) increased LF transiently with a concomitant rise in the cardiac mechanical performance, while dipyridamole induced no change in LF in spite of a marked increase in CF. Isoproterenol at doses of 0.3 and 3×10−8 g/kg induced an increase in LF to 119±4 and 167±20% (mean ±SE); norepinephrine, 0.3 and 3×10−7 g/kg, to 118±4 and 141±13%; ES at 5 and 20 Hz, to 135±11 and 167±10%, respectively. Peak responses of LF correlated with changes in LVSP (r=0.59,n=51,P<0.001), CF (r=0.53,n=51,P<0.001), PP(r=0.49,n=51,P<0.001) but not with changes in HR (r=0.27,n=51, 0.05<P<0.10). Cardiac pacing also showed a poor correlation between the changes in LF and HR under the same LVSP within the changes in HR up to 134% of control value (r=−0.12,n=17,P>0.50). It is concluded that LF is independent of changes in HR, and increased LF after CA or ES may be caused mainly by an augmented propulsive force.

Effects of experimental coronary ligation on pH and lactate concentration in cardiac lymph

Abstract Changes in pH and lactate concentration in the cardiac lymph and arterial blood were studied after ligation of the left coronary artery of the dog. After the coronary ligation, pH of the cardiac lymph dropped significantly accompanied by a rise in the lactate concentration, while the pH and lactate concentration of the arterial blood did not change throughout the experiments. This fall in pH in the cardiac lymph may reflect changes in the interstitial fluid of the ischemic myocardium.

Dopaminergic Receptors in the Coronary Arteries

ABSTRACT The purpose of the present study was to analyse the mechanisms of action of dopamine on the coronary circulation. Dopamine increased coronary blood flow in anesthetized dogs. The increase was not abolished by propranolol but enhanced by phentolamine. The dopamine-induced coronary vasodilatation under alpha and beta adrenoceptor blockade was significantly attenuated by haloperidol which did not affect the coronary vasodilator action of acetylcholine, adenosine and papaverine. When treated with indomethacin after both alpha and beta blockade the dopamine-induced increase in coronary blood flow was strongly inhibited. It was considered that dopamine stimulated alpha and beta adrenoceptors, and specific receptors as well in the coronary arteries. A possible involvement of prostaglandin El in the regulation of coronary circulation was also suggested.

Effects of dihydroergotamine methanesulfonate on the microcirculation of the rat cremaster muscle

SummaryEffects of dihydroergotamine on the microcirculation of the rat cremaster muscle were investigated microscopically using colour photographic technique. 1.Dihydroergotamine 10−4 g/ml constricted arterioles of the rat cremaster.2.Dihydroergotamine 10−4 g/ml produced a significant contraction of venules.3.Dihydroergotamine 10−4 g/ml markedly inhibited the contractile response of noradrenaline 10−6 g/ml on arterioles of the rat cremaster. The results suggest that dihydroergotamine has an appreciable vasoconstrictive action, especially upon venules, and that dihydroergotamine also has an adrenergic alpha-receptor blocking action.By means of highly sensitive negative colour film we obtained a satisfactory photograph of the rat cremasters circulation.