Satoru Murao

Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap.

To investigate the mechanism of atrial flutter in human beings, effects of atrial pacing and extrastimulation on flutter cycle length were studied. In four cases, properly timed extrastimuli shortened the F-F interval after the extrastimulus without affecting the stimulus-encompassing interval. The width of the excitable gap ranged from 14 to 25 percent of the basic flutter cycle length (mean +/- standard deviation 20.4 +/- 4.1). Entrainment to rapid atrial pacing was demonstrated in each case. The width of the entrainment zone nearly coincided with that of the excitable gap in each case. In 16 days, atrial flutter was induced by electrical stimulation after an obstacle was placed between the superior and the inferior venae cavae according to Rosenblueth and Garcia Ramos. In 11 dogs, extrastimuli shortened the F-F interval next to the stimulus-encompassing interval as in the clinical study. The excitable gap, measured in six dogs, ranged from 15 to 24 percent of the basic flutter cycle length (mean 20.6 +/- 3.0). Entrainment was observed in six dogs studied and, during entrainment, the atrial activation sequence was almost the same as that during the basic flutter cycle. It is concluded that shortening of the F-F interval next to the stimulus-encompassing interval that is not affected favors macro-reentry as the mechanism of atrial flutter in human beings.

Plasma levels of 6-keto-prostaglandin F1α in normotensive subjects and patients with essential hypertension

To assess the pathophysiological role of prostacyclin in essential hypertension, plasma levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable, nonenzymatic metabolite of prostacyclin, were assayed in 25 patients with essential hypertension and 25 age-matched normotensive subjects. Supine plasma levels of 6-keto-PGF1 alpha were 270 +/- 14 (SE) in normotensive subjects and 203 +/- 14 pg/ml in the patients with essential hypertension. The difference was statistically significant (p less than 0.001). There was a significant negative correlation between plasma levels of 6-keto-PGF1 alpha and systolic blood pressure (r = 0.44, P less than 0.002), diastolic blood pressure (r = 0.55, p less than 0.001), or mean blood pressure (r = 0.56, p less than 0.001) in the pooled subjects. The same relationship was found in the hypertensive patients. There was no definite relationship either between plasma levels of 6-keto-PGF1 alpha and plasma renin activity (PRA) in the supine position, or between changes in plasma levels of 6-keto-PGF1 alpha and changes in PRA after 60 min of upright posture. These results indicate that circulating prostacyclin is reduced in patients with essential hypertension as compared to normotensive subjects. This reduction of plasma prostacyclin may participate, in part, in the maintenance of blood pressure elevation in patients with essential hypertension. It is also suggested that upright posture is not sufficient to elevate circulating prostacyclin.

Renal Histological Studies in Patients with Takayasu’s Arteritis

Clinical findings and structural alterations of the kidney in 3 patients with Takayasus arteritis (TA) and associated glomerulonephritis are described. Clinical evidence of renal disease included persistent proteinuria and microscopic hematuria in all patients. Renal histology showed proliferative glomerulonephritis in 2 of the 3 patients. In 1 patient in whom sequential examination of the kidney was possible, glomerular changes had progressed in severity, in parallel with the expansion of arterial damage of TA. Prednisolone therapy induced a complete disappearance of systemic symptoms of TA and an improvement of proteinuria and hematuria. These findings suggest that TA, which quite possibly results from an immune response to disseminated antigen(s), may occasionally induced glomerulonephritis as a part of its histological expression.

Antigen Presentation by Kupffer Cells in the Rat

Sprague-Dawley rats were immunized with liver-specific protein (LSP), and the functions of isolated Kupffer cells, as accessory cells and antigen-presenting cells, were examined. More than 70% of the cells showed phagocytic activity for latex particles. The proliferative response of spleen lymphocytes stimulated with concanavalin A was lost in the absence of macrophages but was restored by the addition of Kupffer cells. In vitro stimulation with LSP induced binding of lymphocytes to Kupffer cells and enhanced 3H-thymidine incorporation when lymphocytes were incubated with Kupffer cells from immunized rats. These results indicated that Kupffer cells can act both as accessory cells and as antigen-presenting cells for LSP.

Reduction of prostacyclin synthesis as a possible cause of transient flow reduction in a partially constricted canine coronary artery.

Coronary blood flow decreases cyclically in a partially occluded coronary artery of anesthetized dogs. Spontaneous aggregation and deaggregation of platelet plugs in the constricted artery have been indicated to be responsible for this phenomenon. A current hypothesis is that platelet aggregation may be determined by a balance between proaggregatory platelet product, thromboxane A2 (TXA2), and antiaggregatory substance, prostacyclin (PGI2). To elucidate the relationship between the cyclical reduction of coronary flow (CRCF) and metabolic alterations of TXA2 and PGI2, we attempted to determine the plasma levels of their stable catabolites, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), in the coronary circulation of 69 dogs. Of 40 cases, 20 cases exhibited CRCF accompanying a significant increase in TXB2 in the coronary sinus (CS) (P less than 0.05) and constant levels of 6-keto-PGF1 alpha in the CS and aorta (Ao). Another 20 cases did not exhibit CRCF that accompanied a marked increase in 6-keto-PGF1 alpha (P less than 0.05) with virtually no change in TXB2 in the CS and Ao. A higher dose of indomethacin (10 mg/kg, i.v.) was capable of evoking CRCF in cases not exhibiting CRCF spontaneously. Under these conditions, a significant decrease in 6-keto-PGF1 alpha was seen both in the CS and Ao compared with lower doses of indomethacin (1 to 3 mg/kg, P less than 0.01), that produced less pronounced reduction of 6-keto-PGF1 alpha without CRCF. Intravenous infusion of PGI2 (0.1 microgram/kg/min.) completely abolished spontaneously and indomethacin-induced CRCF with a marked elevation of 6-keto-PGF1 alpha in the CS and Ao. Although OKY-1580, a TXA2 synthetase inhibitor, relieved spontaneously-evoked CRCF with a marked increase in 6-keto-PGF1 alpha and a slight reduction of TXB2, indomethacin-induced CRCF was not abolished by this agent. These results are consistent with the hypothesis that the reduction of endogenous PGI2 synthesis in the vascular wall is related to the occurrence of CRCF after partial constriction of coronary artery and indomethacin.

Histochemical localization of kallikrein-like Pro-Phe-Arg-naphthylester esterase activity in the rat kidney.

SummaryIn the rat kidney the presence of the kallikrein-like pro-phe-arg-naphthylester esterase activity was demonstrated by a simultaneous coupling azo dye method. The enzyme was identified as a serine-protease because it was inhibited by preincubation with diisopropyl-fluorophosphate and unaffected by sodium iodoacetate. Since kallikrein is a serine-protease and pro-phe-arg-naphthylester is a synthetic and sensitive substrate for kallikrein, the enzyme activity revealed by this method was considered to represent kallikrein, although non-kallikrein esterase activity is not totally excluded. The enzyme activity was localized mainly in the outer stripe of the outer medulla, with focal extensions primarily only in the lower half of the cortex corresponding to the medullary rays.

Recurrent multiple myxomas

one of its leaflets. RA myxoma may be confused with mobile RA thrombus;7 this primary tumor, however, usually is round, has a mottled appearance, and is commonly attached to the interatria septum.’ In most reported cases3-’ the mobile RA thrombus originates from the inferior vena cava or peripheral veins in patients with deep leg vein thrombosis and may be transiently entrapped by the tricuspid valve3 or by a patent foramen ovale’ before it travels to the lungs. Our patient had no history of heart disease; the excised RA thrombus had the gross appearance of a leg vein cast and there was evidence of deep vein thrombosis by venogram, thus confirming the above sequence of events which led to massive pulmonary embolism. Immediate surgery and removal of RA thrombi and of several thrombi from the pulmonary arteries were carried out and the patient had an uneventful recovery. Although the exact frequency of this finding in patients with suspected or impending pulmonary embolism is not known, the identification of RA thromboembolus by 2DE raises important questions regarding diagnostic and therapeutic interventions. Confirmatory cardiac catheterization is probably not necessary and may even be dangerous in these patients.4,’ Intravenous anticoagulation with heparin or streptokinase is probably ineffective and may cause partial dissolution of the thrombus.4,fi In our patient and in two other reported cases,4.7 immediate surgical embolectomy after an RA thromboembolus was identified by 2DE resulted in survival and uneventful recovery of the patient. Without such therapy patients invariably develop massive pulmonary embolism, resulting in a fatal outcome.3-fi Although the RA thrombus in our patient was present for at least 2 days prior to the development of massive pulmonary embolism, urgent surgery should be undertaken without the delay or hazards of catheterization as soon as the RA thromboembolus is detected by 2DE.

Postural changes of vectorcardiogram in defect of the left pericardium.

Effects of postural changes upon the vectorcardiograms (VCGs) of four cases with a defect of the left pericardium (three complete and one partial) were compared to those of 115 control cases. Changes in the direction of a given instantaneous vector brought about by postural changes were significantly larger in cases with a pericardial defect than in controls. By turning to the left lateral position, the magnitude of the maximum leftward force decreased in all cases with complete defect, and increased in the case with partial defect and in 96% of controls. These findings were considered to reflect the increased mobility of the heart in cases with pericardial defect due to the lack of the restraining function of the pericardium.

Resetting of tachycardia cycle by single and double ventricular extrastimuli in recurrent sustained ventricular tachycardia.

In two cases with recurrent sustained ventricular tachycardia (VT) due to re‐entry, the response pattern to extrastimuli during the tachycardia was studied. In each case, right ventricular extrastimuli with longer coupling intervals during VT were followed by fully compensatory pauses and with shorter coupling intervals reset the tachycardia cycle. In one case, a plateau was produced by a single extrostimulus, resembling that seen in the response curve of sinus node automaticity as well as ectopic atrial tachycardia. Two successive stimuli produced three definite zones, i.e., fully compensatory, reset producing a plateau, and progressive prolongation zones with shortening of the coupling intervals between the two stimuli, and terminated the tachycardia with further shortening of the coupling intervals. In conclusion, resetting phenomenon was confirmed on two cases with re‐entrant VT. This phenomenon cannot be used as a criterion to determine the mechanism responsible for VT.

Familial Amyloid Polyneuropathy with Marked Hypertrophy of the Peripheral Nerves

Autopsy findings in a 40‐year‐old male with heredofamilial amyloidosis and polyneuropathy are reported. He had been suffering from progressive autonomic as well as sensorimotor dysfunctions. Prominent amyloid deposit was found in the kidney, heart, thyroid, and testis, and less in the interstitium and small vessels of almost all organs. The peripheral nerves, some showing prominent hypertrophy, were most severely involved by amyloid deposit in a form of stellate mass, which ultrastructurally consisted of radially arranged amyloid filaments. In the hypertrophied nerves and ganglia, in addition to amyloid, massive accumulation of acid mucopolysaccharide (AMPS) was seen filling up the interstitial space, which was the cause of hypertrophy. Ultrastructurally, AMPS was seen as finely granular substance. An extracted amyloid from the kidney showed 8 nm filament on negative staining and was estimated of having a molecular weight of 14,000.