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Biomedical subjects

S Kusachi

Publications and source records attributed to S Kusachi.

At least 91 records · Page 5Linked to original sources
PubMed1989

Coronary flow reserve and oxygen metabolism of the right ventricle.

The flow reserve of the right coronary artery (RCA) and myocardial oxygen extraction are important tractors in any investigation of the mechanisms of impaired right ventricular function. The present study induced brief coronary occlusions and examined the effect on right coronary blood flow in normal dogs, and the effect on myocardial oxygen metabolism in dogs with right ventricular hypertrophy (RVH). Right coronary flow reserve, represented by occlusion duration causing a half maximum dilatation (T1/2), was greater in the RCA than in the left anterior descending coronary artery of normal dogs; 11.4 +/- 2.3 sec vs 5.9 +/- 1.4 sec. Myocardial oxygen extraction ratio (EO2) of the right ventricle (RV), 51.3 +/- 1.6%, was significantly (p less than 0.05) lower than the index of the left ventricle (LV), 60.6 +/- 1.0%, and the extraction of the RV increased significantly in association with an increase of myocardial oxygen demand. In dogs with RVH caused by chronic banding of the pulmonary artery, this dominant oxygen reserve was lost: the EO2 of the hypertrophied RV was high compared with the EO2 of the normal RV (57.3 +/- 3.4% vs 51.3 +/- 1.6%, p less than 0.05), and no further increase in EO2 was observed in the hypertrophied RV in response to the elevation of the myocardial oxygen requirement. Oxygen usage per 100g of the RV for a certain level of overall RV work, rate-pressure product, was significantly (p less than 0.02) lower in the hypertrophied RV (0.00054 mlO2/beat.mmHg) than in the normal RV (0.0012 mlO2/beat.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Factors influencing acute high-grade restenosis in emergency percutaneous transluminal coronary angioplasty for acute myocardial infarction.

We studied the factors which may induce acute high grade restenosis in emergency percutaneous transluminal coronary angioplasty (PTCA). PTCA was attempted in 50 patients with acute myocardial infarction, and the balloon catheter passed successfully across the occlusion site in 47 (94%) of the patients. These 47 patients were analyzed. "Acute restenosis" was defined as a lesion which was revascularized to less than 50% luminal reduction narrowed again to more than 75% luminal reduction 5 min after the balloon inflation. Univariate and multivariate analyses were used for determining factors which significantly influenced acute restenosis. The incidence of at least one restenosis episode was 45%. Multiple regression analysis selected 5 factors associated significantly with an increased rate of acute restenosis: 1) angiographic evidence of dissection, 2) lesion in the right coronary artery (RCA), 3) lack of or insufficient administration of thrombolytic agent preceding PTCA, 4) curved lesion and 5) relatively small balloon/artery diameter ratio. Acute restenosis correlated significantly with late reocclusion. This study indicates that it is important to administer a thrombolytic agent prior to emergency PTCA, and to use an adequately sized balloon to the artery when the acute restenosis occurs by using relatively smaller sized balloon. The present data also demonstrated that patients with RCA and a curved lesion have a relatively high risk of acute restenosis. This study indicates how patients with relatively high risk of acute restenosis may be identified.

Acute Disease↗
PubMed1989

Improvement of reduced coronary vasodilatory response during reactive hyperemia by diltiazem.

This study was performed to reconfirm transiently-reduced vasodilatory responses of the coronary artery in the reactive hyperemic period, and also to study whether an increase in calcium influx into the coronary smooth muscle accounts for the reduced coronary vasodilatory responses. Blood flow in the circumflex coronary artery was measured with an electromagnetic flow transducer in anesthetized open-chest dogs. Two successive occlusions for 3 to 7 s performed in pairs with a brief interval were accompanied by decreasing reactive hyperemia: the maximum reduction of reactive hyperemia appeared when the occlusion period was around 5 s with a 5-s interval. Around 5 s after the release of occlusion, excess arterial inflow almost equaled the blood flow debt incurred during the first occlusion. Pretreatment with diltiazem (150 micrograms/kg), a calcium entry blocker, significantly attenuated the reduction of coronary vasodilatory responses, but glyceryl trinitrate (nitroglycerin) did not affect the phenomenon of coronary reactivity. The results suggest that excess accumulation of calcium in the smooth muscle of small coronary arteries occurred during an early period of post-occlusion hyperemia, which resulted in a reduced vasodilatory reactivity of the vessels to the second ischemic stimulus.

Animals↗
PubMed1989

[Acceleration of the left main coronary artery stenosis following PTCA: a report of a case].

Acceleration of the left main coronary artery (LMCA) stenosis induced by guiding catheter which was used for percutaneous transluminal coronary angioplasty (PTCA) was demonstrated in a 68 years old man with post-infarction angina. He underwent PTCA to a subtotal lesion in the left anterior descending coronary artery (LAD). The LMCA with mild stenosis of 18% reduction of luminal diameter was unchanged during the course of PTCA. The guiding catheter was pushed repeatedly with considerable force for introducing balloon catheter due to the rigid lesion in LAD. Progression of the LMCA stenosis to a 64% was demonstrated at 6 months later angiographic restudy. It was considered that repetitive sliding of guiding catheter through the LMCA caused subangiographic intimal trauma and facilitate subsequent progression of stenosis. We examined the guiding catheter to the LMCA diameter ratio, the angle of the tip portion of the guiding catheter with LMCA, and severity of the target lesion in this case compared with other 27 controls in whom PTCA was performed to the lesion in left coronary artery. No difference of these 3 factors between this case and other 27 controls was obtained. Thus it might be difficult to predict progression of LMCA stenosis by these angiographic factors. Although the incidence of catheter-induced progression of LMCA stenosis was as low as 1 of 160 cases (0.6%) in our experience, it is important to attend to catheter-induced progression of LMCA stenosis and to make an early detection.

Aged↗
PubMed1988

Enhancement of coronary conductance by alpha-human atrial natriuretic polypeptide without effects on myocardial contractility.

The effect of synthetic human atrial 28-amino acid peptide (alpha-human atrial natriuretic polypeptide, alpha-hANP) on coronary circulation and cardiac functions was examined in open-chest dogs. Intravenous injection of alpha-hANP increased coronary and systemic conductance, and coronary and aortic blood flow with a significant fall in blood pressure. Continuous infusion of alpha-hANP into the left anterior descending coronary artery (LAD) increased LAD blood flow in a dose-dependent manner. The linear regression analysis revealed the relationship of logit (changes in mean coronary conductance (delta MCC] = 1.45 x log (coronary plasma concentration of alpha-hANP) + 7.51 (r = 0.87, n = 29). REC50 of alpha-hANP was 5.1 microM, where REC50 was the concentration to increase MCC to a half maximum MCC during reactive hyperemia after a 30-s coronary occlusion. alpha-hANP increased coronary conductance with no changes of myocardial oxygen consumption (MVO2) when blood pressure remained constant. Indices of myocardial contractility measured with a strain gauge arch, myocardial force (F), max dF/dt and LV max dp/dt, were not altered by either bolus intravenous injection or continuous intracoronary infusion of alpha-hANP. These results indicated a direct increase by alpha-hANP of coronary and systemic vascular conductance.

Animals↗
PubMed1987

The effect of cardiac sympathetic nerve stimulation on the right ventricle in canine heart.

The change in coronary hemodynamics during right or left cardiac sympathetic nerve stimulation was studied in anesthetized open chest dogs. No difference in the increasing rate of mean coronary blood flow between right coronary artery (RCA) and left anterior descending coronary artery (LAD) was observed. However the increasing rate of right ventricular systolic pressure X heart rate (RVSP X HR) was greater than that of left ventricle (LV). With phentolamine injection, cardiac sympathetic nerve stimulation showed similar changes as the controls. Beta-stimulation by isoproterenol infusion did not cause different effects on the increasing rate of coronary blood flow between RCA and LAD. These results showed that cardiac sympathetic nerve stimulation increased the double product of the right ventricle (RV) more than that of the LV and the increase was not affected by phentolamine. Moreover, cardiac sympathetic nerve stimulation, either the right or the left, caused the greater effects on the RV compared to the LV mainly through beta-adrenoceptors, and that the response of the RV to increase in oxygen demand was possibly, in part, different from that of the LV.

Animals↗
PubMed1986

Structure-activity relationships for N6-substituted adenosines at a brain A1-adenosine receptor with a comparison to an A2-adenosine receptor regulating coronary blood flow.

A series of 145 N6-substituted adenosines have been screened as inhibitors of the binding of [3H]cyclohexyladenosine to an A1-adenosine receptor in rat brain membranes and the results compared to the potencies of these analogs in increasing coronary blood flow via activation of an A2-adenosine receptor. The A1 receptor shows greater stereoselectivity in the N6 region of the receptor towards asymmetric aralkyl substituents, and shows greater bulk tolerance in the N6 region of the receptor such that it retains affinity for certain N6-tertiary alkyladenosines and N6-cycloalkyladenosines that are inactive at the coronary A2 receptor. At the A1 receptor, the most potent analogs have either aliphatic N6-substituents with four or more methylene residues or have an N6-halophenyl substituent. At the A2 receptor, the most potent analogs have an N6-phenethyl or similar heteroarylethyl substituent. Certain sets or series of analogs appear useful for identifying the subtypes of adenosine receptors involved in physiological functions.

Adenosine↗
PubMed1986

Dog coronary artery adenosine receptor: structure of the N6-aryl subregion.

Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.

Adenosine↗
PubMed1986

N6-substituted N-alkyladenosine-5'-uronamides: bifunctional ligands having recognition groups for A1 and A2 adenosine receptors.

The coronary vasoactivity of N-ethyl-1'-deoxy-1'-(6-amino-9H-purin-9-yl)-beta-D-ribofuranuronamide (NECA, 1) is over 2 orders of magnitude greater than that of adenosine, and the vasoactivity of certain N6-substituted adenosines is as much as 1 order of magnitude greater. Such results suggest that a combination of appropriate modifications at N6 and C-5' might additively augment the agonist potency of adenosine. At low temperatures 1-deoxy-1-(6-chloro-9H-purin-9-yl)-2',3'-O-isopropylidene- beta-D-ribofuranosyl chloride (5), obtained in three steps from inosine, reacts with amines to yield uronamides. The subsequent reaction of such uronamides with amines at elevated temperatures displaces the purine 6-chloro group to yield, after deblocking, N-alkyl(or aryl)-N6-alk(ar)yl-adenosine-5'-uronamides. At the coronary artery A2 receptor the potency of N6-modified analogues of 1 is similar to that of the N6-substituted adenosine, rather than equal to or greater than 1. As agonists in the A2 receptor-mediated stimulation of adenylate cyclase in plasma membranes of PC12 pheochromocytoma cells or human platelets, N6-substituted analogues of 1 are intermediate between the high potency of 1 and the lower potency of the N6-substituted adenosines. At the A1 receptor of rat brain the potency of an N6-substituted analogue of 1 is often greater than that of the corresponding N6-substituted adenosine. At all four receptors, replacing the ethyl group of N-ethyl-N6-3-pentyladenosine-5'-uronamide by larger alkyl groups reduces potency; amides of secondary amines are inactive or have only marginal activity. Analogues of 1 containing a chiral center in the N6 substituent retain the stereoselectivity characteristic of each of the four receptors. Thus, at either A1 or A2 adenosine receptors, adenosine analogues interact with both the N6 and the C-5' receptor regions. However, the effects of N6 and C-5' modifications on potency are less than additive, evidence that the interaction of a substituent with its receptor region influences the interaction of other substituents with their respective receptor regions.

Adenosine↗
PubMed1986

Effect of proximal and distal coronary pressure change on the resistance of stenotic coronary segment.

While dynamic changes in the resistance of stenotic coronary segments were recently proposed by several investigators, the mechanisms of these changes are obscure. This study was conducted to correlate changes in coronary pressure distal to the stenosis to dynamic changes in the stenosis resistance in the canine heart. Coronary pressure distal to the stenosis was raised by either proximal aortic pressure elevation or intracoronary blood infusion distal to the stenosis. The pressure rise resulted in a significant fall in the stenosis resistance. Distal coronary pressure drop induced by phlebotomy or removal of blood from the distal coronary bed caused the reverse effects on resistance. Linear regression analysis revealed a close relationship between changes in distal coronary pressure (delta DCP) and those in resistance of the stenotic coronary segment (delta RL) represented by the following equation; delta RL (dyne X cm-5 X sec X 10(-3)) = 0.50 X [delta DCP (mmHg)]-6.0 X 10(-2), r = 0.86, p less than 0.01. The results suggest that dynamic changes in stenosis resistance appear largely to be a function of the pressure changes distal to the stenosis.

Animals↗
PubMed1986

Hemodynamic effects of labetalol in the dog. Comparative study in the anesthetized open-chest dog and in the conscious dog.

Hemodynamic effects of labetalol, an alpha- and beta-adrenoceptor blocking drug, were investigated in the conscious dog and in the anesthetized open-chest dog. In the conscious dog, intravenous injection of labetalol, in a dose of 0.5 mg/kg, decreased the total peripheral resistance by approximately 20% (P less than 0.01) in association with falls in blood pressure and heart rate. The total peripheral resistance of the anesthetized open-chest dog was not affected by labetalol in the presence of the same extent of blood pressure fall as results of the conscious dog. In contrast, agents which have beta-adrenoceptor blocking effect alone provided substantial elevation of the total peripheral resistance in the anesthetized dog. These results indicate that the different responses of the resistance to labetalol probably result from the vascular alpha-adrenoceptor blocking action, and also show that in the conscious state alpha-adrenoceptor blocking action of labetalol is enhanced in comparison with the effect in the anesthetized open-chest dog.

Adrenergic beta-Antagonists↗
PubMed1985

Dog coronary artery adenosine receptor: structure of the N6-alkyl subregion.

The moderately potent and stereoselective coronary vasoactivity of N6-[1-phenyl-2(R)-propyl]adenosine (1) is the basis for the present study that maps the N6 region of the coronary artery adenosine receptor by means of the structure-coronary vasoactivity relationships of 81 analogues of 1 in the open-thorax dog. Stereoselectivity is a general property of N6-substituted adenosines that have a chiral center adjacent to N6. The activity ratio of 1 to its S diastereomer is 10, the result of the positive interaction with the receptor of the propyl C-3 group of the R diastereomer in combination with the steric hindrance exerted by this group of the S diastereomer. Replacing the benzyl moiety of 1 by an ethyl, phenyl, phenethyl, or naphthyl group lowers potency of the R diastereomer and, accordingly, the R/S ratio. Propyl C-1 of 1 interacts with a receptor region large enough to accommodate three methylene residues and the propyl C-3 residue with a separate region large enough to accommodate two. The receptor subregion that interacts with the propyl C-1 of 1 is more tolerant of bulk and of polar substituents than the subregion that interacts with propyl C-3. Evidence bearing on the possible contribution of N6 to activity, e.g. through hydrogen bonding, is ambiguous. These results support a provisional model of the N6-alkyl subregion.

Adenosine↗
PubMed1985

Effect of adenosine deaminase inhibitors on myocardial reactive hyperaemia following brief coronary occlusions.

Effect of two agents of adenosine deaminase inhibitor, 8-azaguanine and adenine, on myocardial reactive hyperaemia was tested in the anaesthetised open-chest dog. Reactive hyperaemic flow response of the circumflex coronary artery was observed following 5, 10, 15, 20 and 30 s coronary occlusions before, during and after infusion of 8-azaguanine and adenine, which are known as adenosine deaminase inhibitors. Intracoronary infusion of 8-azaguanine and adenine caused the minimum increase in the baseline coronary flow. Both the nucleic acids shifted the dose response curve of adenosine to the left. 8-azaguanine enhanced volume response of flow at all occlusion intervals tested. The infused dose of adenine also intensified volume response of flow after 5, 15, 20 and 30 s occlusions. Fifteen minutes after termination of the nucleic acid infusions, the reactive hyperaemia returned towards control levels. The results suggest that 8-azaguanine and adenine enhance myocardial reactive hyperaemia possibly by inhibiting adenosine deaminase to degradate myocardial interstitial adenosine to inosine.

Adenine↗
PubMed1984

Forskolin potentiates the coronary vasoactivity of adenosine in the open-chest dog.

Forskolin, a plant diterpene, directly stimulates adenylate cyclase and also potentiates receptor-mediated stimulation of this enzyme by many stimulatory--but not inhibitory--agonists. We exploited the potentiating effect of forskolin to test the hypothesis that adenosine initiates coronary relaxation through activation of adenylate cyclase. In six open-chest dogs, intracoronary forskolin infusions which produced plasma concentrations between 0.15 and 0.48 microM barely changed coronary flow and had no effect on cardiac performance or oxygen metabolism, and did not cause hypotension. Under these conditions, the EC50 of adenosine, 0.66 microM (range 1.3-2.4), P less than 0.05. In five of the six dogs, higher doses of forskolin, 0.6-6.3 microM, produced the previously described positive inotropic, chronotropic, and systemic hypotensive effects of this drug. These larger doses of the drug increased coronary flow and MVO2 but decreased oxygen extraction, reflecting a combination of direct and metabolic vasodilation. The potentiation of the vasoactivity of adenosine by forskolin supports the hypothesis that the coronary receptor is an adenylate cyclase stimulatory (Ra or A2) receptor.

Adenosine↗