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Biomedical subjects

Y Kamiyama

Publications and source records attributed to Y Kamiyama.

At least 181 records · Page 10Linked to original sources

Short-term changes in blood ketone body ratio in the phase immediately after liver transplantation.

Arterial blood ketone body ratio was measured after orthotopic liver transplantation in piglets. Ketone body ratio immediately decreased at the beginning of the anhepatic phase and was rapidly restored to the normal levels within 30 min after the revascularization of the allograft. Serum lactate and pyruvate levels increased in anhepatic phase and gradually decreased after revascularization. Changes in the lactate and pyruvate levels were always preceded by changes in ketone body ratio. In the case of transplantation after 12-hr-preservation of the allograft, ketone body ratio failed to maintain normal levels after transplantation, resulting in a high mortality. It is suggested that the elevation of decreased ketone body ratio is prerequisite for the normalization of the deranged metabolic state after liver transplantation, and that ketone body ratio provides an accurate means to assess the initial metabolic function of the allograft.

Animals↗

Fluorometric study for the noninvasive determination of cellular viability in perfused rat liver.

Pyridine nucleotide fluorescence in perfused rat liver for the noninvasive determination of donor graft viability was investigated in relation to other metabolic indices, such as NAD concentration, adenine nucleotides, and mitochondrial phosphorylative activity. The amplitude between oxidation and reduction levels (RxA) in fluorometric trace, and the slope or the velocity of the trace curve from oxidation to reduction (RxV) were determined by the measurement of fluorescence from NAD(P)H, using a new fluorometric device, RxA and RxV decreased proportionally to the duration of preservation period (6, 12, 24, 48 hr) in simple cold storage. Other values of hepatic cell viability, such as total adenine nucleotides, energy charge, and mitochondrial phosphorylation rate, were simultaneously measured and also decreased proportionally to the duration of preservation period. There were close positive correlations between the percentage of RxA and NAD concentration (r = 0.724, p less than 0.01), between the percentage of RxA and total adenine nucleotides (r = 0.887, p less than 0.01), between the percentage of RxV and energy charge (r = 0.715, p less than 0.01), and between the percentage of RxV and phosphorylation rate/cytochrome a(+a3) (r = 0.837, p less than 0.01). These results suggest that this fluorometric method can provide an accurate noninvasive evaluation of donor graft viability--and, unlike the present indices of energy metabolism, it may be applied to evaluate the primary nonfunctioning graft prior to transplantation.

Adenine Nucleotides↗

Influence of hemodilution on hepatic energy metabolism in rat.

The effects and safety limits of acute hemodilution on hepatic energy status were investigated in relation to arterial blood ketone body ratio and hepatic energy charge in a hemodilution rat model. As long as the hematocrit value was maintained above 20%, ketone body ratio and energy charge level at 6 h after hemodilution remained at the same levels as those of the sham-diluted groups. However, when hematocrit value was less than 15%, the ketone body ratio markedly decreased from the control value of 0.686 +/- 0.044 to 0.278 +/- 0.048 (p less than 0.001), and energy charge decreased from the control value of 0.856 +/- 0.012 to 0.0806 +/- 0.011 (p less than 0.01). From these results, it was suggested that hemodilution exerts no influence on the energy status of the liver as long as hematocrit is maintained above 20%.

Adenine Nucleotides↗

Acute responses of blood ketone body ratio following devascularization and revascularization of rabbit liver.

Acute changes associated with anhepatic and revascularized state were analyzed in relation to mitochondrial energy metabolism in rabbits. Fifteen minutes after the induction of anhepatic state, the ketone body ratio in the arterial blood decreased markedly from 0.833 to 0.229. The ketone body concentration also decreased to 24% of the normal value. The blood ketone body ratio and concentration remained low during the next 45 min. Pyruvate and lactate levels and the pyruvate/lactate ratio in the arterial blood changed very little during the 60-min anhepatic state. In a revascularization model following a 15-min anhepatic state, the ketone body concentration rose rapidly and then declined gradually, finally attaining a constant level at 30 min. The decreased blood ketone body ratio recovered to 0.55 at 30 min, and achieved steady state thereafter. Mitochondrial phosphorylative activity and hepatic energy charge showed almost normal levels 60 min after revascularization following the 15-min anhepatic state. These results indicate that the rapid metabolic alterations associated with the anhepatic and revascularized state can be accurately determined by measuring the arterial blood ketone body ratio, and they suggest that the ketone body ratio may serve as a convenient parameter for the evaluation of liver viability in pathological states such as operative ischemia or liver transplantation.

3-Hydroxybutyric Acid↗

Acute gastric ulceration in rats with obstructive jaundice with special reference to gastric mucosal blood flow.

The mechanism of acute gastric ulceration in rats with obstructive jaundice was investigated in terms of the changes in the gastric mucosal blood flow, and the effect of vagotomy on ulceration was examined. 188 Sprague-Dawley rats weighing about 250 g were prepared and divided into 4 groups as follows; control group (sham operation), jaundiced group (ligation of the bile duct), vagotomized group (vagotomy with pyloroplasty), jaundiced and vagotomized group (simultaneous ligation of the bile duct and vagotomy with pyloroplasty). Two weeks after the operation, water immersion and restraint stress procedures were performed in these 4 groups. The gravity of acute gastric ulcerations was calculated by ulcer index. The gastric mucosal blood flow was measured by hydrogen clearance technique. The following results were obtained: In control group, ulcer index was increased and gastric mucosal blood flow was decreased after the stress procedures. The jaundiced group showed significantly higher ulcer index and early significant decrease of gastric mucosal blood flow after the stress procedures compared to the control group. The vagotomized group showed significantly decreased ulcer index after the stress procedures compared to the control group, however, the gastric mucosal blood flow showed almost the same values as the control group. The jaundiced and vagotomized group showed significant decrease of ulcer index and improvement of decrease of gastric mucosal blood flow compared to the jaundiced group. These results indicated that the gastric mucosal blood flow plays an important role in the occurrence of acute gastric ulceration in rats with obstructive jaundice, and vagotomy might be useful to prevent them by maintaining gastric blood flow in obstructive jaundice.

Animals↗

[Surgical management of perianal lesions in Crohn's disease].

Perianal lesions associated with Crohn's disease are often intractable and require surgical intervention. Among 28 patients surgically treated in our department, 16 patients manifested perianal complications consisted of four periproctal abscesses, eight anal fistulas, three skin tags and one anal fissure. The incidence of perianal lesions was higher in ileocolic type than in colic and ileal type. In half of our patients perianal lesions preceded the diagnosis of Crohn's disease, and they often gave the important clue for the diagnosis. The perianal lesions seemed to be independent of the activity of the intestinal lesions. The surgical treatments for the perianal lesions were performed on 13 patients and the results were satisfactory in most cases. But the results were very poor in four patients with rectal involvement. Two of them were obliged to undergo proctectomy because of the severely diseased anorectal lesions. Therefore radical surgery should be considered in patients whose perianal lesions are quiescent, and the severity of the rectal lesion was considered to be the major factor which decides the prognosis of the patients.

Abscess↗

Effect of hepatic artery embolization on the adenylate energy charge level and the redox state of the cirrhotic liver.

Hepatic energy charge ((ATP + 1/2ADP)/(ATP + ADP + AMP)) and arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate) were measured after hepatic artery embolization in carbon-tetrachloride-induced cirrhotic rats. In normal livers, energy charge slightly decreased at 3 h and returned to normal levels at 6 h. By contrast, in cirrhotic livers, energy charge was drastically decreased at 3 h after embolization and was not completely recovered at 6 h. Blood ketone body ratio, reflecting hepatic mitochondrial redox (NAD+/NADH) state, also decreased at 3 h after embolization in both groups, and its recovery was not observed in cirrhotic group at 6 h.

Adenine Nucleotides↗

Short-term changes in blood ketone body ratios in the phase immediately after hepatic artery embolization: their clinical significance.

Changes in arterial and hepatic venous blood ketone bodies were investigated following transcatheter hepatic artery embolization (THAE) in patients with hepatocellular carcinoma. Acetoacetate/ beta-hydroxybutyrate ratio (ketone body ratio) in arterial blood was positively correlated with those of hepatic venous blood (r = 0.960, p less than 0.001), which reflects the mitochondrial redox potential in the embolized lobe. Nine cirrhotic patients were classified into three groups according to the changes in arterial blood ketone body ratio following THAE: Type A without decrease to below 0.7; Type B with a transient decrease to below 0.7, followed by its restoration within 5 hours; and Type C with decrease to below 0.7 without recovery within 5 hours. There were no serious complications in Type A and B patients. By contrast, severe sepsis and hepatic failure developed in Type C patients, possibly due to the extended embolization of both lobes. It is suggested that THAE can be successfully performed even in severely cirrhotic patients, as long as the embolized area is restricted to one lobe. In addition, changes in arterial blood ketone body ratios can give early information about the likely consequences of the THAE procedure just performed.

3-Hydroxybutyric Acid↗

Influence of obstructive jaundice on acute gastric ulcer, intragastric pH and potential difference in rats.

To elucidate the influence of obstructive jaundice on the process of acute ulceration of the stomach under stress loading and to investigate the preventative effect of vagotomy, a series of experimental studies were carried out using SD rats. Animals were divided into four groups: Control, jaundice, vagotomy and jaundice with vagotomy. Each group was subjected to the water immersion-restraint stress and changes in the potential difference of gastric mucosa (PD), the intragastric pH (pH) and the score of ulcer index at sacrifice (UI) were measured. The process of acute ulceration under the stress loading was shown to be accelerated by the weakening of defensive factors in the case of obstructive jaundice. To monitor changes of pH and PD was found to be useful to predict the manifestation of gastric lesion. Vagotomy seemed to be partly effective to prevent the ulceration evidenced by lowering aggressive facter (an increase of pH), but it may also decrease the defensive factor because the vagotomy produced a significant lowering of PD.

Animals↗

[Experimental study on acute ulceration in association with obstructive jaundice--with special reference to the effect of biliary drainage on gastric mucosal blood flow and energy kinetics].

The mechanism of acute ulceration in association with obstructive jaundice was studied experimentally by measurement of gastric mucosal blood flow and energy kinetics. The effect of biliary drainage was also evaluated. Three hundred thirty nine SD male rats weighing about 250 gr were grouped as follows; control group--Sham operation, obstructive jaundice group-2 weeks after ligation and dissection of the choledochus, and biliary drainage group-- A silicone tube was inserted and opened after 2 weeks of obstructive jaundice. All the animals were stressed by water immersion and ulcer index, gastric mucosal blood flow, gastric mucosal energy kinetics and liver function were assessed. The obstructive jaundice group showed significant higher ulcer index and lower gastric mucosal blood flow and energy kinetics than the control group. These factors of the biliary drainage group started to improve soon after biliary drainage and reached to the levels of the control group. In conclusion, reduction of defensive factors caused by jaundice was proved to play an important role in acute ulceration associating obstructive jaundice. Biliary drainage improves both gastric mucosal blood flow and gastric mucosal energy kinetics so that it is preventive against acute ulceration.

Acute Disease↗

Clinical significance of hippurate-synthesizing capacity in surgical patients with liver disease: a metabolic tolerance test.

Changes in the amount of hippurate synthesized and excreted in the urine after 1.5 gm benzoate loading (intravenous hippuric acid test [HAT]) in patients with liver disease before surgery were studied in relation to arterial blood ketone body ratio (acetoacetate/beta-hydroxybutyrate) (BKBR), reflecting energy status of the liver. In these patients, the HAT values for 120 minutes were decreased significantly (1.088 +/- 0.129 gm, n = 9; 1.071 +/- 0.258 gm, n = 7; 1.258 +/- 0.126 gm, n = 10; in cirrhosis with liver tumor, cirrhosis with esophageal varix, and obstructive jaundice, respectively) as compared with the value in patients without liver disease (1.829 +/- 0.093 gm, n = 16, P less than 0.01). The correlation coefficient of the BKBR and the HAT value was 0.766, which was higher than that of the BKBR and albumin or the BKBR and choline esterase (r = 0.532 and r = 0.646, respectively). Serum levels of glutamic-oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, leucine aminopeptidase, total and direct bilirubin, creatinine, and blood urea nitrogen were not correlated with the HAT values. Because hippurate is synthesized in liver mitochondria by the continuous supply of adenosine triphosphate through mitochondrial oxidative phosphorylation, HAT is considered to be a test that evaluates the energetic capacity of the liver to manage a metabolic load imposed on it.

Adult↗

Changes in coenzyme Q level in mitochondria of cirrhotic rat liver.

In the cirrhotic rat liver induced by carbon tetrachloride and phenobarbitone, the concentrations of mitochondrial Coenzyme Q were measured in comparison with other respiratory components. The concentration of cytochrome a(+a3) and Coenzyme Q significantly increased in the cirrhotic liver, without any changes in the ratio of Coenzyme Q to cytochrome a(+a3). It is suggested that such increase of Coenzyme Q plays an important role as one of the adaptive responses to compensate for the prolonged metabolic overload on the mitochondrial respiratory assembly. Also, from the findings that the concentrations of cytochrome a(+a3) in the mitochondria of cirrhotic liver increase concomitant with the severity of cirrhosis, it is suggested that the rise of Coenzyme Q levels may be one of the indicators for the decreased functional reserve capacity in liver cirrhosis.

Animals↗

Sequential changes in blood concentrations of fuels in relation to arterial blood ketone body ratio after 70% hepatectomy in rabbits.

The changes in arterial blood levels of glucose, free fatty acids, ketone bodies, and amino acids were investigated after 70% hepatectomy in rabbits in relation to the changes in adenylate energy charge of the remnant liver and ketone body ratio of arterial blood. Hepatic energy charge decreased to 0.767 +/- 0.008 within 24 h (p less than 0.001), and arterial blood ketone body ratio decreased to 0.415 +/- 0.041 within 12 h (p less than 0.001). Plasma free fatty acid concentrations increased to about twice the original values within 12 h (p less than 0.01), total amino acid concentrations also doubled within 24 h (p less than 0.01), and blood glucose levels decreased to below 100 mg/dl at 12 and 24 h (p less than 0.05). Afterward, at 96 h postoperatively (p.o.), blood ketone body ratio and energy charge levels were restored to near normal levels with the normalization of blood glucose, plasma free fatty acids, and plasma amino acids. These findings suggest that the decreased energy charge of the remnant liver concomitant with a fall in blood ketone body ratio may be the basis of the sequential changes in the blood concentration of fuels after massive hepatectomy.

Alanine↗

Relationship of glucose intolerance and indocyanine green clearance to respiratory enzyme levels in human cirrhotic liver.

The relationship of glucose intolerance and indocyanine green clearance to respiratory enzyme levels in liver mitochondria was studied along with standard liver function tests in 40 patients (8 cirrhosis, 19 cirrhosis with hepatoma, 13 non-cirrhotic with hepatoma). There was a negative correlation between cytochrome a(+a3) concentrations and phosphorylative activity per unit of cytochrome a(+a3) (r = -0.75, p less than 0.01), but no correlation between ICG-K and cytochrome a(+a3) concentrations. Cytochrome a(+a3) concentrations in cirrhotic patients with linear oral glucose tolerance pattern, characterized with no return toward normal glucose levels within 120 minutes after an oral glucose load, increased to 1.45 +/- 0.11 (10(-10) mol/mg of protein) compared with 0.90 +/- 0.07 in cirrhotic patients with parabolic OGTT pattern, characterized with a return toward normal glucose levels within 120 minutes (p less than 0.01) (0.82 +/- 0.02 in control patients without liver diseases). The former had high operative mortality regardless of ICG-K value and the latter had virtually uneventful clinical courses. It was suggested that increased cytochrome a(+a3) concentrations and impaired glucose tolerance might be responsible for decreased hepatic functional reserve and poor prognosis in cirrhotics.

ATP Synthetase Complexes↗

Pathophysiology of hemorrhagic shock. A model for studying the effects of acute blood loss in the rat.

A model of acute blood loss in rats with a reproducible mortality rate over a wide range of body weights was developed by withdrawing various amounts of fixed blood volume per 100 g body weight via the left common carotid artery and observing the survival of the animals. Younger (lighter) animals survived the bleeding longer than older (heavier) animals. As early as 70 min following the shock episode there was evidence of acute tubular necrosis in kidney proximal tubules and focal centrilobular necrosis in the liver. The 84%, 50%, or 16% body weight - mortality line was: V84 = -0.17 BW + 3.25; V50 = -0.18 BW + 3.16; or V16 = -0.18 BW + 3.01 in animals ranging from 250 to 400 g body weight (where V = bleeding volume ml/100 g body weight, BW = body weight in grams X 10(-2). To produce the same mortality rate, the bleeding volume per unit body weight decreased with increased body weight. On the other hand, the bleeding volume per total blood volume or per unit body surface area increased with increased body weight. The body weight-mortality line is a useful method to calculate the bleeding volume to produce predetermined mortality rate. This method can be easily applied to various pathophysiological and metabolic studies on the nature of acute blood loss as well as in the treatment of acute blood loss.

Age Factors↗