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Biomedical subjects

M Uechi

Publications and source records attributed to M Uechi.

At least 19 recordsLinked to original sources

Identification and functional role of beta-adrenergic receptor subtypes in primate and rodent: in vivo versus isolated myocytes.

We determined the relationship between the beta 1- and beta 2-adrenergic receptor subtypes in isolated myocytes and their physiological responsiveness in chronically instrumented conscious baboons and rats. In conscious baboons, isoproterenol (ISO) (0.02 microgram/kg) increased left ventricular (LV) dP/dt by 89 +/- 6.7% from 2898 +/- 370 mmHg/s and only by 13 +/- 3.3% from 2491 +/- 146 mmHg/s after beta 1-adrenergic receptor blockade, indicating that the predominant physiological response was mediated by beta 1-adrenergic receptors. Decreases in mean arterial pressure (-11 +/- 0.5 mmHg v -16 +/- 4.6 mmHg) and coronary vascular resistance (-3.1 +/- 0.4 v -3.6 +/- 0.4 mmHg/ml/min) induced by ISO were not different before and after beta 1-blockade, indicating that beta 2-adrenergic receptors were not blocked. In conscious rats, ISO (0.4 microgram/kg) increased LV dP/dt by 50 +/- 4.9% from 13252 +/- 2002 mmHg/s and only by 10 +/- 3.9% from 10793 +/- 1364 mmHg/s after beta 1-adrenergic receptor blockade: whereas decreases in mean arterial pressure induced by ISO were not different before and after beta 1-blockade (-19 +/- 2.4 mmHg v -16 +/- 2.2 mmHg), i.e. very consistent with the physiological responses in baboons. In vitro studies of isolated myocytes, using radioligand binding with 125I-cyanopindolol (125I-cyp) and the subtype beta 1-selective antagonist betaxolol and the beta 2-selective antagonist ICI 118551 indicated that the beta 1/beta 2 ratio of rat myocytes was 92/8: whereas baboon myocytes were more equally distributed (59/41). Thus, in both species the preponderance of effects of ISO on ventricular function was beta 1-adrenergic receptor mediated, which is consistent with the beta 1/beta 2 ratio in rat myocytes but not in baboon myocytes, where a significant fraction of beta 2-adrenergic receptors does not appear to exert an effect on conctractility in vivo.

Adrenergic beta-Antagonists

Adverse effects of chronic endogenous sympathetic drive induced by cardiac GS alpha overexpression.

To study the physiological effect of the overexpression of myocardial Gsalpha (protein levels increased by approximately threefold in transgenic mice), we examined the responsiveness to sympathomimetic amines by echocardiography (9 MHz) in five transgenic mice and five control mice (both 10.3 +/- 0.2 months old). Myocardial contractility in transgenic mice, as assessed by left ventricular (LV) fractional shortening (LVFS) and LV ejection fraction (LVEF) was not different from that of control mice at baseline (LVFS, 40 +/- 3% versus 36 +/- 2%; LVEF, 78 +/- 3% versus 74 +/- 3%). LVFS and LVEF values in transgenic mice during isoproterenol (ISO, 0.02 micrograms/kg per minute) infusion were higher than the values in control mice (LVFS, 68 +/- 4% versus 48 +/- 3%; LVEF, 96 +/- 1% versus 86 +/- 3%; P < .05). Norepinephrine (NE, 0.2 micrograms/kg per minute) infusion also increased LVFS and LVEF in transgenic mice more than in control mice (LVFS, 59 +/- 4% versus 47 +/- 3%; LVEF, 93 +/- 2% versus 85 +/- 3%; P < .05). Heart rates of transgenic mice were higher than those of control mice during ISO and NE infusion. In three transgenic mice with heart rates held constant, LV dP/dt rose by 33 +/- 2% with ISO (0.02 micrograms/kg per minute) and by only 13 +/- 2% in three wild-type control mice (P < .01). NE (0.1 micrograms/kg per minute) also induced a greater effect on LV dP/dt in the three transgenic mice with heart rates held constant compared with three wild-type control mice (65 +/ 8% versus 28 +/- 4%, P < .05). Pathological and histological analyses of older transgenic mouse hearts (16.0 +/- 0.8 months old) revealed hypertrophy, degeneration, atrophy of cells, and replacement fibrosis reflected by significant increases in collagen volume in the subendocardium (5.2 +/- 1.4% versus 1.2 +/- 0.3%, P < .05) and in the cross-sectional area of myocytes (298 +/- 29 versus 187 +/- 12 micron2, P < .05) compared with control mouse hearts. These results suggest that Gsalpha overexpression enhances the efficacy of the beta-adrenergic receptor-Gs-adenylyl cyclase signaling pathway. This in turn leads to augmented inotropic and chronotropic responses to endogenous sympathetic stimulation. This action over the life of the animal results in myocardial damage characterized by cellular degeneration, necrosis, and replacement fibrosis, with the remaining cells undergoing compensatory hypertrophy. As a model, this transgenic mouse offers new insights into the mechanisms of cardiomyopathy and heart failure and provides a new tool for their study.

Animals

Mitral valve protrusion assessed by use of B-mode echocardiography in dogs with mitral regurgitation.

OBJECTIVE: To examine our hypothesis that changes of the mitral valve in dogs with mitral regurgitation lead to various degrees of protrusion of the cusp in individual dogs in systole. DESIGN: Assessing the mitral protrusion, using B-mode echocardiography in dogs with mitral regurgitation. ANIMALS: 33 dogs with chronic mitral regurgitation and 40 clinically normal dogs. PROCEDURE: The mitral valve was imaged in the right parasternal left ventricular long-axis view, and we measured the height (H) from the coaptation point or tip of the protruded cusp to the mitral annular plane. When the tip of the protruded cusp was located beyond the mitral annular plane extending into the left atrium, H was expressed as negative values. RESULTS: The H in clinically normal dogs was 3.7 +/- 0.8 mm. In dogs with mitral regurgitation, the mitral cusp protruded toward the left atrium to various degrees, and H was -0.7 +/- 1.9 mm (range, 2.9 to -5.0 mm). The 2 dogs in the latter group with the lowest H (-5.0 and -4.5 mm, respectively) presented typical mitral flail on B-mode images. The indices of left atrial and ventricular dimension (left atrial dimension/aortic dimension and left ventricular end-diastolic dimension/body weight, respectively) were significantly higher than those in the clinically normal dogs and were negatively correlated with H. CONCLUSION: The mitral valve in individual dogs with mitral regurgitation has different degrees of protrusion. The degree of protrusion might be related to the hemo-dynamic condition in mitral regurgitation.

Animals

Evaluation of urinary enzymes in dogs with early renal disorder.

We investigated urinary N-acetyl-beta-D-glucosaminidase NAG (EC 3.2.1.30), gamma-glutamyl transpeptidase gamma-GTP (EC 2.3.2.2) and glycyl-prolyl dipeptidyl aminopeptidase GP-DAP (EC 3.4.14.5) in dogs with heartworm disease and renal failure. In the renal failure dogs, the NAG, gamma-GTP and GP-DAP index were significantly higher than those in the healthy dogs. In the heartworm disease dogs with normal chest X-rays (HW I), none of the enzyme values was significantly different from those of the healthy controls. In the dogs with heartworm disease showing abnormal heart shadows on their chest X-rays (HW II), enzyme values were significantly higher than those in the healthy dogs (P < 0.01) and the HW I dogs (P < 0.01). Thus, these urinary enzymes tests are available for the early detection of renal disorders.

Acetylglucosaminidase

Circadian variation of urinary enzymes in the dog.

Circadian variations of N-acetyl-beta-D-glucosamidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) were examined in dogs. Urine and blood were collected at 4-hr intervals from adult mongrel dogs (11 males, 11 females) weighing between 7 and 13 kg. The collected urine and blood were used to measure creatinine, NAG and gamma-GTP. The amount of urine was significantly higher (p < 0.05) during the period from 12:00 to 16:00. Creatinine clearance did not show any characteristic variations and creatinine excretion was significantly higher (p < 0.05) during the period from 8:00 to 16:00. No characteristic variations were observed in the amounts excreted, activity, or NAG and gamma-GTP creatinine index. There were high correlations between creatinine excretion and creatinine clearance (r = 0.693), gamma-GTP excretion and gamma-GTP creatinine index (r = 0.724), NAG excretion and NAG creatinine index (r = 0.878), and between the NAG and gamma-GTP creatinine index of each 4-hr specimen and the NAG and gamma-GTP excretion of the 24-hr specimens. These results suggest the diagnostic usefulness measuring enzyme activity in non-periodically collected urine.

Acetylglucosaminidase

Prevalence of valvular regurgitation in normal beagle dogs detected by color Doppler echocardiography.

We examined the prevalence and characteristics of valvular regurgitation in 20 normal beagle dogs with no cardiac murmur by color Doppler echocardiography. The prevalence of pulmonary, mitral, aortic and tricuspid valvular regurgitation was 75%, 15%, 10%, and 0%, respectively. The peak flow velocity of pulmonary, mitral and aortic regurgitation was 57.1 +/- 18.5 cm/sec (mean +/- SD), 89.8 cm/sec (mean) and 96.5 cm/sec, respectively. The peak velocity of regurgitant flow was considered characteristically low, as the calculated pressure gradient derived from the modified Bernoulli equation (pressure gradient = 4 x velocity) was not as high as the normal pressure gradient existing across each valve. We consider that, in the evaluation of the characteristics of regurgitation in dogs, regurgitant signals having low peak velocity can be regarded as being physiological or trivial regurgitation.

Animals

A case report of surgical treatment of a dog with atrioventricular septal defect (incomplete form of endocardial cushion defect).

A 3-month-old female collie was diagnosed as having atrioventricular septal defect with ostium primum atrial septal defect (PASD). The diagnosis was made by echocardiographic observation of the PASD and goose-neck deformity on left ventriculogram. The PASD was treated surgically with a patch graft under cross-circulation cardiopulmonary bypass (CC). The PASD was identified above the ventricular septum after right atriotomy. The patch graft was sutured along the fibrous tissue of the tricuspid annulus on the ventricular side of the PASD to avoid injuring the conduction system. After the operation, cardiac function and renal output were well preserved, but the dog died 33 hr later. At postmortem examination, a mitral cleft was identified.

Animals

Peritoneal dialysis using a recycling system in dogs.

In this study, Recirculation Peritoneal Dialysis (RPD) apparatus using a pump to circulate the dialysate was devised and its dialysis efficiency was investigated. In the experiment, 15 mongrel dogs with body weights of 6.6 +/- 0.7 kg were used. The surgery to induce azotemia was performed on the dogs, a disk catheter for drainage was placed between the liver and diaphragm, and a straight catheter for infusion was placed on the abdominal side of the bladder. RPD was conducted using 2 l of dialysate containing 1.3% glucose, and the dialysate was circulated by a pump through the peritoneal cavity and the dialysate chamber at the circulation rates of 30, 60, 90 and 120 ml/min. RPD was conducted for 3 hr and the clearances of urea nitrogen, creatinine, inorganic phosphorus and potassium were recorded every hour. The clearances in RPD became higher with an increase in the circulation rate. Although RPD requires two catheters in the peritoneal cavity, it has no appreciable technical difficulty in handling and is considered to be easier than hemodialysis. RPD enabled higher dialysis efficiency to be achieved in a short time compared with conventional peritoneal dialysis. It seems reasonable to conclude that RPD is a useful new dialysis technique for animals.

Animals

Machine perfusion of isolated kidney at 37 degrees C using pyridoxalated hemoglobin-polyoxyethylene (PHP) solution, UW solution and its combination.

To preserve isolated kidney normothermically, PHP containing UW components were evaluated as perfusates. Kidneys were flushed out by Lactate Ringer solution immediately after isolation from mongrel dogs, and then connected to the perfusion circuit which consists of a preservation box, a reservoir of perfusate, a membrane oxygenator and a drive unit. PHP containing 140 mEq/l of Na+ and 4 mEq/l of K+ (PHP(E)), UW solution (UW) and UW components added PHP(E) were prepared and adjusted at pH 7.4 prior to use. Temperature and perfusion pressure were controlled at 37 degrees C and 100 mmHg, respectively. During 12 hour perfusion, remarkable changes in pH were seen in UW group and PHP group while higher oxygen consumption was noted in PHP(E)+UW group than that in PHP(E) group. The histological findings showed moderate damages of tubular epithelial cells and maintaining normal glomerular structure in PHP(E)+UW while severe damage of both tubulus in UW group were seen. There was no edematous degeneration in both UW and PHP(E)+UW groups, however, it was seen in PHP(E) alone. It was suggested that components of UW solution have positive effect on normothermic machine perfusion with PHP(E) solution.

Adenosine