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Biomedical subjects

S Kusachi

Publications and source records attributed to S Kusachi.

106 records · Page 6Linked to original sources

Simple technique for measuring regional contractility by a modified strain guage arch.

A simple modification of a commercially available gauge arch, namely the addition of pins to effect mechanical couplings to heart muscle rather than suturing, results in an isometric myocardial force sensor which is easy to insert, stable and relatively atraumatic to the myocardium. Compressing the pins by means of a machinist's vernier caliper which is removed after the sensor is implanted, insures controlled muscle stretch. Tests in open-chest dogs show that force sensed by this gauge is little affected by changes in heart rate, left ventricular end-diastolic pressure or aortic pressure, but faithfully reflects the inotropic effects of isoproterenol or propranolol. Thus, the modified strain gauge arch is sensitive to changes in contractility but not to changes in preload or afterload.

Animals↗

Pericardial superfusion to measure cardiac interstitial adenosine concentration.

The steady-state concentration of adenosine in pericardial superfusates, [Ado]SS, may estimate the concentration in the cardiac interstitium. As reaching a steady state may sometimes require many minutes, the concentration at an earlier time is often used as an index of [Ado]SS. The latter assumes that the rate of approach to [Ado]SS is uniform and insensitive to perturbations of cardiac oxygen usage (MVO2). In 11 open-chest dogs superfusate adenosine rose at a rate (+/- SD) of 0.53 +/- 0.99/min to an [Ado]SS of 68 +/- 32. The mean rate of equilibration has a very large coefficient of variation, indicating substantial dog-to-dog variation. In five dogs the rate of equilibration during the second of successive superfusions was significantly lower than the first. Raising MVO2 by cardiac pacing or isoproterenol infusion changed neither the rate of equilibration nor [Ado]SS. Aortic constriction or propranolol slowed equilibration but had no effect on [Ado]SS. Thus superfusate adenosine concentration early in the course of equilibration seems an unreliable index of [Ado]SS. That interventions that change MVO2 do not change [Ado]SS from control means either that [Ado]SS fails to reflect the concentration in the vicinity of the coronary resistance vessels or, alternatively, that adenosine does not regulate coronary blood flow.

Adenosine↗

Ligand selectivity of dog coronary adenosine receptor resembles that of adenylate cyclase stimulatory (Ra) receptors.

Adenosine receptors on the surface of coronary myocytes initiate coronary relaxation, but events subsequent to receptor occupancy are uncertain. We assayed the coronary vasoactivity of receptor-selective adenosine analogs in open chest dogs to test the hypothesis that the coronary adenosine receptor is an adenylate cyclase stimulatory (Ra) receptor. The potency order was: ethyl adenosine-5'-uronamide greater than cyclopropyl adenosine-5'-uronamide greater than 2-chloroadenosine greater than N6-[R(-)-1-phenyl-2-propyl] adenosine (R-PIA) greater than N6-cyclohexyladenosine greater than adenosine greater than S-PIA. Such a hierarchy of activity resembles that of the Ra receptors of thyroid and aortic myocyte adenylate cyclases and of tracheal smooth muscle relaxation. The potency order R-PIA greater than adenosine and the stereoselective coronary vasoactivity of R-PIA suggest that the coronary receptor may be a hybrid receptor which contains the "N6 site" typical of inhibitory (Ri) receptors in addition to the "5'-uronamide site' which expresses Ra activity.

Adenosine↗

Decrease in myocardial oxygen extraction with aortic constriction in the dog.

In the open-chest dog constriction of the descending thoracic aorta, which raises central aortic pressure by 30-80 mmHg, increases cardiac oxygen usage (MVO2) and coronary blood flow (CBF) but reduces heart rate and myocardial oxygen extraction [(A-V)O2]. Pacing tachycardia superimposed on aortic constriction further increases MVO2 and CBF but does not alter (A-V)O2. Atropine or vagotomy abolishes the effect of aortic constriction on (A-V)O2, whereas vagal stimulation in the presence of alpha- and beta-adrenergic blockade reduces (A-V)O2. L-propranolol and phenoxybenzamine fail to modify the effect of aortic constriction on (A-V)O2. These results indicate that aortic constriction reduces (A-V)O2 by eliciting parasympathetically-mediated coronary vasodilation.

Animals↗

Right and left ventricular oxygen metabolism in open-chest dogs.

A comparison of blood flow and myocardial O2 consumption (MVO2) in the right and left ventricles was made in 21 open-chest dogs. Simultaneous measurements were made of left anterior descending (LAD) and right coronary arterial blood flow and of O2 saturation in the coronary sinus and in from one to four anterior cardiac veins. Blood flow was greater in the LAD than in the right coronary artery, 87 +/- 5 vs. 46 +/- 3 ml.min-1.100 g-1. Similarly, the O2 saturation was 51 +/- 3% in the anterior cardiac veins and 40 +/- 1% in the coronary sinus. In a subset of seven dogs, the O2 saturation in blood from anterior cardiac veins varied substantially from vein to vein. The mean MVO2 was greater for the left than for the right ventricle, 8.6 +/- 1.4 vs. 4.0 +/- 0.3 ml O2.min-1,100 g-1. Increases in LAD flow with no increase in O2 extraction accounted for enhanced MVO2 of the left ventricle due to pacing, isoproterenol, or methoxamine. In contrast, pacing, isoproterenol, or constriction of the pulmonary artery increased MVO2 of the right ventricle by both augmented O2 extraction and a rise in right coronary blood flow. We conclude that right coronary arterial blood flow is lower per 100 g tissue and is less dependent on MVO2 than is LAD blood flow. The heterogeneity of O2 saturation in anterior cardiac veins suggests that regional differences in MVO2 may exist.

Animals↗

Enhancement of myocardial reactive hyperemia and adenosine-induced coronary vasodilation by dilazep, a new adenosine potentiator.

The effect of N,N'-bis[3'-(3",4",5"-trimethoxybenzoyloxy)-propyl]hexahydro-1, 4-diazepine (dilazep) on myocardial reactive hyperemia and coronary vasodilatory potency of adenosine was studied in the anesthetized open-chest dog. Dilazep injected i.v. was detected in the pericardial effusate, suggesting that the drug could enter the interstitial space of the heart. A threshold dose of dilazep increased vasodilatory action of exogenous adenosine. The dose of dilazep enhanced compensation for flow debt during myocardial reactive hyperemia caused by 5-, 10-, 15-, 20- and 30-s coronary occlusions, respectively, whereas peak flow rate was increased in response to only 5- and 10-s occlusions by dilazep, respectively. The results obtained suggest that dilazep potentiates the effect of endogenous adenosine which is released during ischemia and also suggest that adenosine plays important role in myocardial reactive hyperemia.

Adenosine↗

Comparative effects of heart rate and aortic blood pressure on MVO in the anesthetized open-chest dog.

Comparative effects of heart rate and aortic blood pressure on myocardial oxygen consumption (MVO2) were studied in anesthetized open-chest dogs. The left coronary artery was perfused through the external shunt with blood from the left common carotid artery. Heart rate was changed with the left atrial pacing and the constriction of the descending thoracic aorta was utilized to elevate the proximal aortic blood pressure (BP). The left ventricular enddiastolic pressure was insignificantly changed with the atrial pacing and with the aortic constriction. With the constant BP (100 +/- 5 mmHg), and unit increase in heart rate per minute augmented MVO2 by 0.027 ml/min/100 Gm of left ventricular muscle, while one mmHg elevation of BP caused 0.15 ml increment in MVO2 per minute per 100 Gm of left ventricular muscle under the constant heart rate (115 +/- 5 beats/min). Therefore an unit change in BP caused five- to six-fold greater increase in MVO2 compared with that in heart rate, indicating extremely important roles of BP in MVO2.

Animals↗

Increase in the calculated resistance of anatomically fixed stenosis in vitro in association with decrease in distal resistance.

The effects of changes in distal resistance on stenotic resistance were studied in vitro. Physiological saline was passed through the left carotid artery obtained from the dog, flexible rubber tubing, or through solid polyethylene tubing with a constant perfusion pressure or with a constant flow rate. Various stenotic resistances were established using a screw type constrictor and the distal resistance was varied by allowing physiological saline to pass through either a 23 gauge hypodermic needle (high peripheral resistance) or 23 and 20 gauge needles (low peripheral resistance ). For arteries with anatomically fixed stenosis, the calculated resistance was increased in association with reduction of the distal resistance. The stenotic resistance in the flexible rubber tubing changed in the same manner as that of the carotid artery, while the solid polyethylene tubing showed no significant stenotic resistance changes due to altering the distal resistance. These findings suggest that the stenotic resistance change of the artery correlates with the elasticity of the vessel wall and also indicate that resistance values were of little usefulness for evaluating the effects of vasodilating stimuli on the vessel segment with a significant stenosis.

Animals↗

Effect of graded coronary constriction on the flow reserve in regional myocardium in dog.

Effects of coronary constriction on the flow reserve of regional myocardium were studied in the anesthetized open-chest dogs. Regional myocardial blood flow (RMBF) was continuously measured using heated crossthermocouple method. Left circumflex coronary artery (LCX) was constricted gradually with a screw type constrictor. The coronary constriction decreased subendocardial myocardial blood flow, while subepicardial myocardial blood flow was not affected until reactive hyperemia in LCX nearly disappeared. Recovery and arrival to peak flow rate of RMBF following the release of 15-second's occlusion of LCX were progressively delayed with an increase in the constriction, especially in the subendocardial myocardium. Repayment of flow debt, however, was remained relatively well since the duration of reactive hyperemia in RMBF was prolonged by an increment of the constriction. From these findings, it might be concluded that in the heart with coronary stenosis recovery from ischemia was caused by prolonged duration of reactive hyperemia, and is suggested that the time required for recovery from ischemia or ischemic abnormalities after the cessation of stress might be an important marker for the severity of coronary insufficiency.

Animals↗

Instability of reference diameter in the evaluation of stenosis after coronary angioplasty: percent diameter stenosis overestimates dilative effects due to reference diameter reduction.

PURPOSE: To examine changes in the reference segment luminal diameter after coronary angioplasty. METHODS: Sixty-one patients with stable angina pectoris or old myocardial infarction were examined. Coronary angiograms were recorded before coronary angioplasty (pre-angioplasty) and immediately after (post-angioplasty), as well as 3 months after. Artery diameters were measured on cine-film using quantitative coronary angiographic analysis. RESULTS: The diameters of the proximal segment not involved in the balloon inflation and segments in the other artery did not change significantly after angioplasty, but the reference segment diameter significantly decreased (4.7%). More than 10% luminal reduction was observed in seven patients (11%) and more than 5% reduction was observed in 25 patients (41%). More than 5% underestimation of the stenosis was observed in 22 patients (36%) when the post-angioplasty reference diameter was used as the reference diameter, compared with when the pre-angioplasty measurement was used and more than 10% underestimation was observed in five patients (8%). CONCLUSION: This study indicated that evaluation by percent diameter stenosis, with the reference diameter from immediately after angioplasty, overestimates the dilative effects of coronary angioplasty, and that it is thus better to evaluate the efficacy of angioplasty using the absolute diameter in addition to percent luminal stenosis.

Adult↗

Time-dependent increases in syndecan-1 and fibroglycan messenger RNA expression in the infarct zone after experimentally induced myocardial infarction in rats.

BACKGROUND: Syndecan-1 and fibroglycan, heparan sulphate proteoglycans, play important roles in extracellular matrix formation via their biological functions. OBJECTIVE: To examine experimentally the sequential changes in syndecan-1 and fibroglycan messenger RNA (mRNA) expression after acute myocardial infarction. MATERIALS AND METHODS: The left coronary arteries of male Sprague-Dawley rats were ligated and the hearts were excised on days 1-14, 28 and 42. Syndecan-1 and fibroglycan mRNA expression in the infarct and non-infarct zones and in sham-operated hearts was determined by reverse transcriptase-polymerase chain reaction. Amplified products were quantified by densitometry of the electrophoresed bands stained with ethidium bromide and standardized relative to the glyceraldehyde 3-phosphate dehydrogenase or beta-actin mRNA expression. Northern hybridization was also performed in the infarct and non-infarct zones on day 3. RESULTS: Expression both of syndecan-1 and of fibroglycan mRNA began to increase on day 2. The expression attained maximum levels on day 3. The maximum levels of syndecan-1 and fibroglycan expression were, respectively, sevenfold and fivefold the preligation level and the level in the sham-operated hearts. The levels remained elevated until day 14, whereupon they declined gradually, returning to the control levels by around day 42. Northern blotting also demonstrated that there was an increased expression both of syndecan-1 and of fibroglycan mRNA in the infarct compared with that in the non-infarct zone on day 3. CONCLUSION: Our results demonstrated that there are sequential increases in the expression both of syndecan-1 and of fibroglycan mRNA in the infarct zone after experimentally induced myocardial infarction in rats, suggesting that these proteoglycans play some role in the pathological course of infarction.

Animals↗

Relationship between body mass index and anti-hypertensive efficacy of doxazosin according to a survey of Japanese patients.

In this cross-sectional study, we surveyed a population of 101 hypertensive patients in Japan to determine the efficacy of the blood pressure lowering effect of alpha 1-blockers in relation to their body mass index (BMI). We found that doxazosin was frequently administered to obese hypertensive patients; many patients treated with doxazosin were taking concomitant medication. We also demonstrated that the higher the dose of doxazosin, the lower the ambulatory blood pressure measured in the out-patient clinic. Doxazosin showed a more favourable blood pressure lowering effect in patients with a higher BMI. These results suggest that anti-hypertensive drugs are useful when used in obese patients receiving multiple concomitant medications. These patients would normally be considered to show a poor response to anti-hypertensive treatment. Furthermore, we expect the alpha 1-blocker doxazosin to demonstrate a dose-dependent effect in obese patients with hypertension.

Adult↗

Coronary flow reserve after coronary intervention in similar in patients with preserved viability in previous myocardial infarction and in those with angina pectoris.

The relationship between coronary flow reserve (CFR) and viability in the infarcted myocardium has not been fully clarified. We measured coronary blood flow velocity immediately after coronary intervention (with percutaneous transluminal coronary angioplasty [PTCA] or stenting) in 38 patients with previous myocardial infarction and preserved viability and 48 with angina pectoris. CFR was calculated and was similar between the two patient groups. No differences in the incidence of post-intervention CFR > 2.0 were detected; there were no differences in post-intervention CFR between patients with preserved myocardial viability and those with angina pectoris who underwent PTCA. Coronary stenting reduced the percentage diameter stenosis in both groups compared with PTCA and slightly increased the post-intervention CFR. No differences were, however, detected in post-intervention CFR between patients with preserved myocardial viability and those with angina pectoris who underwent additional stenting. These results reveal that in patients with preserved myocardial viability, post-intervention CFR was restored to values similar to those in patients with angina pectoris.

Aged↗

Coronary artery spasm demonstrated by coronary angiography in a patient with acute myocarditis resembling acute myocardial infarction; a case report.

A 59-year-old male with acute myocarditis presenting symptoms resembling acute myocardial infarction underwent urgent coronary angiography due to difficulties in determining a diagnosis. Coronary artery spasm was demonstrated in the proximal right and left anterior descending coronary arteries. The spasm varied from time to time and lesion to lesion. But no fixed occluded lesion was observed. Predischarge coronary angiography showed no abnormal findings. Histological findings of the biopsy specimen from the left ventricle were consistent with myocarditis. The findings of this case indicate that a coronary artery spasm may aggravate the myocardial damage occurring in acute myocarditis. Urgent coronary angiography and endomyocardial biopsy are important to make the diagnosis of myocarditis in patients presenting symptoms resembling acute myocardial infarction.

Coronary Angiography↗