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Biomedical subjects

T Matsuki

Publications and source records attributed to T Matsuki.

At least 73 records · Page 4Linked to original sources

Angiotensin-converting enzyme inhibitors and the kallikrein-kinin system.

The role of plasma kinin in the hypotensive mechanism of angiotensin-converting enzyme (ACE) inhibitors in essential hypertensive patients and in a dog myocardiac ischemic model is discussed. Both an increase in plasma kinin and a decrease in plasma angiotensin II might contribute to the hypotensive effects of ACE inhibitors in a normal-renin group. In a low-renin group, the hypotensive mechanism of this drug may be mainly the increase in plasma kinin levels. The augmentation of urine volume and urinary sodium excretion may also be related to the hypotensive effects of ACE inhibitors, and this mechanism might be explained by the renal blood flow increase and augmented activity in the renal kallikrein-kinin system. In a dog myocardial ischemia model, when an apparent myocardial ischemia occurred in the constricted group, plasma kinin levels in coronary sinus blood increased significantly. Following infusion of kinin into the left main coronary artery, 0.1 ng/kg/min of kinin for 5 min did not cause any change in plasma kinin levels in the artery or coronary sinus. A dose of 10 ng/kg/min of kinin for 5 min produced a significant elevation in plasma kinin in the coronary sinus from 12.8 to 142 pg/ml without any change in plasma kinin in the artery. However, such a level of kinin had no significant effect on coronary circulation, myocardial metabolism, or ECG ST segment in either group. Thus, the role of increased kinin in this dog model still remains unclear. Further studies including the administration of ACE inhibitors or bradykinin antagonist will be necessary to reach conclusions about the role of kinin in the heart.

Angiotensin-Converting Enzyme Inhibitors↗

Oxypurinol limits myocardial infarct size in closed chest dogs without pretreatment.

The authors tested whether allopurinol or oxypurinol could limit infarct size when treatment was started just prior to reperfusion and continued until sacrifice. In closed chest, anesthetized dogs, a branch of the left coronary artery was reversibly occluded for 90 mins followed by 24 h of reperfusion. Fifteen minutes prior to reperfusion, dogs received a bolus of either allopurinol (10 dogs), or oxypurinol (nine dogs), 10 mg/kg intravenously, followed by a 24 h infusion, 55 mg/kg/day. Eleven control dogs received equal volumes of saline. Investigators were blinded to the identity of the agent. Hearts were removed 24 h after reperfusion. Arrhythmias for 30 mins after reperfusion were quantitated. Oxypurinol caused 28% less of the risk zone to infarct for any level of collateral flow than that seen in the controls. This difference was significant. Allopurinol-treated hearts averaged only 18% less infarction and did not achieve significance. Ventricular arrhythmias and mortality did not differ among the three groups. Therefore, unlike allopurinol, oxypurinol with continued administration can limit tetrazolium-indicated necrosis in the dog heart in the absence of pretreatment.

Allopurinol↗

Chronic whole body sympathectomy fails to protect ischemic rabbit hearts.

We determined whether chronic chemical sympathetic denervation could protect the rabbit heart against ischemia. Rabbits received 10 mg/kg 6-hydroxydopamine (6-HD) twice during the first week, then 100 mg.kg-1.wk-1 for the following 7 wk. After this interval the rabbits were anesthetized, the chests were opened, and in each a coronary branch was occluded for 45 min followed by reperfusion for 3 h. Collateral flow was determined with radioactive microspheres during coronary occlusion. Flow to the ischemic myocardium of the 6-HD group (0.06 +/- 0.03 ml.min-1.g-1) was not significantly different from that in the control group (0.04 +/- 0.02 ml.min-1.g-1). Infarct size was determined with triphenyltetrazolium chloride staining. Average infarct size calculated as a percentage of risk zone was similar in the 6-HD and control groups (59 +/- 15 and 60 +/- 12%, respectively). We conclude that chronic chemical sympathectomy does not induce collateral growth in the rabbit heart. Furthermore, endogenous catecholamines do not contribute to injury in the ischemic rabbit heart.

Animals↗

The effect of inotropic dose of dobutamine during reperfusion on myocardial infarct size.

We examined whether dobutamine infusion during reperfusion modifies myocardial infarct size in a rabbit ischemia-reperfusion model. Prior to the infarct size study, the hemodynamic response to dobutamine 5, 10, and 15 micrograms/kg/min i.v. was evaluated in the rabbit model. Ten micrograms/kg/min of dobutamine increased the left ventricular dp/dt max by 34.0 +/- 4.9% (n = 7) and the myocardial blood flow from 0.86 +/- 0.16 to 2.19 +/- 0.57 ml/min/g without change in the collateral blood flow (n = 4). The heart rate, systolic and diastolic blood pressures were elevated by only 4.7 +/- 1.0%, 9.4 +/- 3.0%, and 8.0 +/- 3.7%, respectively (n = 7). In the infarct size study, a coronary branch was occluded for 30 min and then reperfused. Seventy-two hours after reperfusion, the myocardium supplied by the occluded artery (area at risk, AAR) and the infarcted area were determined by fluorescent particles and histology (hematoxylin-eosin and modified Mallory's staining), respectively. In the dobutamine treated group (DB group), 10 micrograms/kg/min of dobutamine were infused for 30 min starting immediately after reperfusion, and a comparable volume of saline was infused in the control group. Hemodynamic parameters and the size of AAR were comparable in the control and DB groups. Myocardial infarct size, expressed as the percentage of AAR, was 45.1 +/- 3.9% in the control (n = 11) and 40.2 +/- 2.4% in the DB group (n = 10), which was not significantly different. These findings indicated that the inotropic dose of dobutamine administered during reperfusion did not cause myocardial necrosis by disturbing the recovery process of the myocardium from ischemic injury.

Animals↗

[Pulmonary embolism as a complication in neurosurgical patients].

The overall incidence of pulmonary embolism (PE) among neurosurgical in-patients, whose ages ranged from 23 to 80, was 0.7%. Our report here is based on five cases of patients with PE. Four of these five patients were over 50 years of age. They had been admitted because of such reasons as brain tumor, spinal cord injury, intracerebral hematoma, and venous sinus thrombosis. Deep vein thrombosis (DVT) was seen in four but none were diagnosed before they had developed PE. Decreased level of consciousness and prolonged bed rest appeared to be common risk factors for PE. Mean duration between admission and onset of PE was 31 days. Although non-specific, tachycardia, tachypnea and hypoxemia were the most common signs and symptoms. As a definitive diagnostic procedure, pulmonary angiography was performed in most of cases. One patient required surgical embolectomy and others were treated with anticoagulation or fibrinolytic agents. In order to prevent recurrent thromboembolic phenomena, ligation of the inferior vena cava was a useful mode of treatment when anticoagulation was not indicated. And this approach seemed to be valid in most neurosurgical patients. We conclude that PE and DVT were not uncommon complications among Japanese neurosurgical patients and they can be treated successfully in collaboration with a cardiovascular surgeon if the diagnosis can be made correctly.

Adult↗

Pressure-flow characteristics and nutritional capacity of coronary veins in dogs.

To examine the hemodynamic interdependence of coronary arteries and veins, great cardiac vein (GCV) and left anterior descending (LAD) coronary artery flows of dogs were measured. Although they were not different under base-line conditions, 42.9 +/- 4.1 and 34.9 +/- 5.2 ml/min, respectively, LAD occlusion caused only a 56% decrease in GCV flow, whereas peak GCV flow during reactive hyperemia consistently underestimated peak LAD flow by nearly 40%. The measured hemodynamic data were very closely predicted by a simple model that assumed the presence of a low-resistance venous collateral anastomotic pathway between the GCV and veins outside the LAD territory. The resistance of the venous collaterals averaged 9.9 +/- 3.0% of LAD resistance. Therefore, GCV flow does not solely represent LAD collateral flow when the LAD is occluded, nor is it a reliable indicator of changes in LAD perfusion patterns. Nutritional myocardial perfusion assessed with 133Xe washout decreased from 0.86 +/- 0.16 to 0.13 +/- 0.02 ml.min-1.g-1 after LAD occlusion, whereas retroperfusion of the GCV with arterial blood enhanced washout by 85% to 0.23 +/- 0.03 ml.min-1.g-1 (P less than 0.005). Retroperfusion was inefficient, however, since only 10% of the isotope injected into the GCV gained access to the myocardium.

Animals↗

Decrease of palmitoyl-CoA elongation in platelets and leukocytes in the patient of hereditary methemoglobinemia associated with mental retardation.

Effect of the deficiency of NADH-cytochrome b5 reductase on fatty acid elongation was studied in the platelets and leukocytes taken from a patient of hereditary methemoglobinemia associated with mental retardation. The activity of fatty acid elongation was determined by measuring the incorporation of [2-14C]malonyl-CoA into palmitoyl-CoA. The de novo biosynthesis of fatty acids was blocked by the addition of phosphotransacetylase, and the elongation system could be assayed in the homogenates separated from de novo biosynthesis. As compared to normal subjects approximately 40% decrease of fatty acid elongation was observed both in the platelets and leukocytes from the patient.

Acyl Coenzyme A↗

Sympathetically induced myocardial ischaemia causes the heart to release plasma kinin.

A recently developed highly sensitive radioimmunoassay method for detecting plasma kinin was used to re-evaluate the results of previous studies, in which plasma kinin had been measured with a bioassay method. To clarify the mechanism of plasma kinin release in global myocardial ischaemia the left main coronary artery was cannulated using a Griggs type autoperfusing cannula after pentobarbital anaesthesia in open chest dogs. The animals were divided into a non-coronary constricted group (n = 4) and a moderately coronary constricted group (n = 7). Cardiac sympathetic nerve stimulation (10 V, 4 Hz, 2 ms duration) was given to both groups. Haemodynamic recordings and blood samples were taken before and after coronary constriction as well as after sympathetic nerve stimulation. The arterial and coronary sinus plasma kinin concentrations were determined with the new radioimmunoassay method. After sympathetic nerve stimulation apparent myocardial ischaemia occurred and the plasma kinin concentration in coronary sinus blood increased significantly in the constricted group. In the non-constricted group, however, myocardial ischaemia did not appear and no significant change in coronary sinus plasma kinin concentrations was seen. These findings show that there was a pronounced release of plasma kinin from the heart when apparent myocardial ischaemia occurred.

Animals↗

Pulmonary artery connection in the Fontan procedure. Flexible polytetrafluoroethylene conduit for expansion.

From clinical experiences with the Fontan operation in six cases, a few practical contrivances and operative steps are described. We stress that meticulous care should be taken not to cause any stenotic complication in the outflow tract toward the pulmonary artery, particularly by traction of the right atrial appendage only to achieve a direct anastomosis. Conduit repair would be necessitated by cases in order to expand the indicative criteria vertically as well as horizontally. For conduit material, we used consecutively nonvalved polytetrafluoroethylene that was reinforced by handmade stainless steel wire ring (Gore-Tex, Inc) or by spirally built-in stent (IMPRA, Inc). The latter was eventually useful in obtaining natural curving of the conduit without kinking or compression. Some contrivances in anastomosing a conduit were also proposed to achieve an excellent result. We believe these practical contrivances will serve for expansion of the indicative criteria and promise improved operative outcome.

Adolescent↗