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Biomedical subjects

M Iwase

Publications and source records attributed to M Iwase.

At least 181 records · Page 10Linked to original sources
PubMed1990

Hemodynamic mechanisms of antianginal action of calcium channel blocker nisoldipine in dynamic exercise-induced angina.

To investigate the mechanism of antianginal action of the calcium channel blocker nisoldipine and to determine the reproducibility of the clinical and hemodynamic events induced by supine leg exercise, 30 patients with stable effort angina pectoris were studied. They were divided into two groups; one group of 19 patients received a single 10-mg dose of nisoldipine orally, and the other group of 11 patients received a single dose of placebo orally. Chest pain was induced in all of 30 patients during the control exercise test. After nisoldipine administration, chest pain was not induced in 13 of 19 patients and was of lessened severity in five patients with the same work load as those performing control exercise. ST segment at peak exercise showed less severe depression after nisoldipine. Systemic vascular resistance was reduced by 38% (p less than 0.001) at rest and 22% (p less than 0.001) at peak exercise, and coronary vascular resistance was reduced by 31% (p less than 0.01) at rest and 18% (p less than 0.01) at peak exercise. Pulmonary artery wedge pressure fell from 6 +/- 1 to 3 +/- 1 mm Hg (p less than 0.001) at rest and from 28 +/- 3 to 11 +/- 2 mm Hg (p less than 0.001) at peak exercise. Coronary sinus flow at rest and myocardial oxygen uptake both at rest and during exercise was not modified by nisoldipine. However, coronary sinus flow at peak exercise increased significantly from 219 +/- 24 to 249 +/- 31 ml/min (p less than 0.01) after nisoldipine, and myocardial oxygen uptake was not significantly changed despite decreased coronary vascular resistance. The clinical and hemodynamic events induced by the exercise during invasive studies (except pulmonary artery wedge pressure at rest) were reproducible after placebo administration. Our data demonstrate that increased coronary blood flow could be the major mechanism of the antianginal action of nisoldipine in supine leg exercise-induced angina.

Adult↗
PubMed1990

Suppression of the renin-angiotensin system induced by streptozotocin treatment in neonatal spontaneously hypertensive rats.

We studied whether or not neonatal streptozotocin (STZ) treatment would alter mean arterial pressure (MAP) and blood pressure regulating factors in conscious and unrestrained spontaneously hypertensive rats (SHR). Neonatal STZ administration to SHR resulted in type 2 diabetes mellitus with reduced MAP and heart rate. Plasma glucose was markedly increased in these diabetic animals and was inversely correlated with MAP. In the diabetic SHR, the hypotensive responses to captopril (SQ) or enalapril, administered intravenously, were diminished, regardless of preceding administrations of vasopressin V1-antagonist (AVPA) or hexamethonium (C6), when compared to findings in control rats. In contrast, the C6-induced hypotension was similar in rats with diabetes and control animals. AVPA led to no decrease in MAP in either group. Hypotensive responses to SQ following AVPA and C6 inversely correlated with the plasma levels of glucose in the diabetic group. The combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system and vasoconstrictive action of vasopressin (AVP) abolished the differences in MAP between the groups. Pressor and bradycardic responses to intravenous noradrenaline, angiotensin II and AVP were practically identical in the diabetic and control SHR. Urinary aldosterone excretion rate was not altered by neonatal STZ treatment. In conclusion, a decrease in MAP in SHR with neonatal STZ treatment may be attributed to the suppressed pressor activity of RAS.

Angiotensin II↗
PubMed1990

[Determinants of left ventricular inflow: the relation of the transmitral velocity profile to loading conditions].

To clarify the factors controlling left ventricular inflow, hemodynamics and Doppler-derived indices were analyzed in six anesthetized open-chest dogs with intact pericardia. Low molecular dextran was intravenously infused at 1 L/hr. During rapid infusion, an electrocardiographic lead, left ventricular pressure curve, and a transmitral Doppler signal were recorded at various heart rates produced by right atrial pacing. In five of the six dogs, the relationship of the ratio of peak velocity during atrial contraction to that during rapid filling (A/R) and left ventricular end-diastolic pressure (LVEDP) showed a non-linear quadratic curve concave to the LVEDP axis. Data from the ascending and descending limbs of the A/R-LVEDP relationship were subjected to stepwise multiple linear regression analysis (criterion variables: A/R; explanatory variables: peak dP/dt, maximum left ventricular pressure, time constant T, minimum left ventricular pressure, LVEDP, and heart rate). In both limbs, the A/R correlated positively with maximum left ventricular pressure (left ventricular afterload) and negatively with LVEDP (left ventricular preload). The time constant T was selected as a positive correlate only in the ascending limb. The transmitral flow velocity profile is determined in a complex manner by multiple factors, including left ventricular loading conditions and heart rate, as well as the left ventricular diastolic property. It was suggested that the A/R is not altered unidirectionally by the changes in cardiac function and loading conditions, but that it returns to the initial value accompanied by systolic and diastolic cardiac dysfunction.

Animals↗
PubMed1990

Electron microscopic studies of medullary synaptic inputs to vasopressin-containing neurons in the hypothalamic paraventricular nucleus.

We have observed the ascending projections from the lower brain stem to the magnocellular vasopressin-like immunoreactive (VP-LI) neurosecretory neurons in the paraventricular nucleus (PVN) using electron microscopy. The tissues were prepared by a double labeling technique combining anterograde tracing after iontophoretic injection of wheat germ agglutinin-coupled horseradish peroxidase (WGA-HRP) in the A1 group (lateral reticular nucleus in the medulla oblongata) with VP immunocytochemistry. Both the WGA-HRP-labeled and the unlabeled axon terminals made synaptic contacts with VP-LI cell bodies and processes in the PVN. This indicates a direct synaptic influence of medullary A1 group on the secretory activity of the VP-containing neurons in the hypothalamic paraventricular nucleus.

Animals↗
PubMed1989

Early detection of myocardial ischemia by myocardial free fatty acid extraction in patients with exercise-induced angina pectoris.

This study investigated whether the measurement of plasma free fatty acids (FFAs) could assist in the early detection of exercise-induced myocardial ischemia. Fifteen subjects with effort angina pectoris underwent angina-limited supine bicycle ergometer exercise testing. Myocardial FFA extraction decreased significantly from 22.8 +/- 3.1% at rest to 7.7 +/- 1.5% at peak exercise (p less than 0.05). Myocardial lactate extraction showed no significant change between rest and peak exercise. After control exercise testing, 8 subjects were given a single oral dose of nilvadipine (6 mg) and then again underwent exercise testing for the same duration. Nilvadipine lessened or abolished chest pain and there was less depression of the ST segment at peak exercise. Furthermore, myocardial FFA extraction showed no significant change between rest and peak exercise after nilvadipine administration. These results suggest that myocardial FFA extraction can be used to assess the presence of exercise-induced myocardial ischemia at an earlier stage than myocardial lactate extraction.

Angina Pectoris↗
PubMed1989

Evaluation by exercise Doppler echocardiography of maintenance of cardiac output during ventricular pacing with or without chronotropic response.

To examine the effectiveness of activity-initiated rate-responsive pacing, this study assessed the increases in stroke volume and cardiac output during randomized treadmill exercise in rate-responsive and fixed-rate ventricular (VVI) pacing in 10 patients. Stroke volume index and cardiac index were determined by suprasternal Doppler measurements. Compared with the findings during VVI pacing, the rate-responsive pacing was associated with (1) prolongation of exercise duration (8.0 +/- 4.0 vs 7.3 +/- 3.6 minutes, p less than 0.05); (2) greater exercise-induced positive chronotropic response (mean maximal heart rate 127 +/- 12 vs 78 +/- 15 beats/min, p less than 0.001); (3) smaller increase in stroke volume index (38 +/- 10 vs 50 +/- 11 ml/m2, p less than 0.001), and (4) greater increase in cardiac index (4.7 +/- 1.1 vs 3.9 +/- 1.0 liters/min/m2, p less than 0.001). A significant correlation was observed between age and percent increase in stroke volume index during VVI pacing (p less than 0.05). These findings indicate that VVI pacing increased stroke volume more than did rate-responsive pacing, especially in younger patients, but the increase in cardiac output was less than that seen with rate-responsive pacing due to the absence of chronotropic response. Accordingly, an activity-sensing, rate-responsive pacemaker can effectively increase the heart rate, significantly augment cardiac output and extend the duration of exercise.

Adult↗
PubMed1989

Noninvasive detection of exercise-induced markedly elevated left ventricular filling pressure by pulsed Doppler echocardiography in patients with coronary artery disease.

To assess the accuracy of the exercise-induced decrease in the ratio of peak flow velocity in atrial systole to that in early diastole (A/E) for predicting an elevation of left ventricular filling pressure, supine bicycle ergometer exercise testing was performed in 27 consecutive patients with coronary artery disease. Doppler-derived transmitral flow velocities were recorded at rest and immediately after exercise. A/E decreased during exercise in 16 patients (group A) and increased in 11 (group B). Pulmonary artery wedge pressure (PAWP) increased notably from 7 mm Hg at rest to 26 mm Hg at peak exercise in group A (p less than 0.001). In contrast, PAWP increased slightly from 6 mm Hg to 10 mm Hg in group B (p less than 0.05). The cardiac index at peak exercise in group A was significantly lower than that in group B (p less than 0.05). These findings suggest that patients with an exercise-induced decrease in A/E might not increase their cardiac output. A significant negative correlation between PAWP and A/E was observed in patients with PAWP over 20 mm Hg (r = -0.74; p less than 0.005). The exercise-induced decrease in A/E showed a sensitivity of 100%, a specificity of 73%, and a predictive accuracy of 85% in detecting patients with PAWP over 20 mm Hg. These findings show that Doppler recordings of transmitral flow velocities during dynamic exercise can provide useful information concerning exercise-induced left ventricular dysfunction associated with markedly elevated filling pressures.

Cardiac Output↗
PubMed1989

The important role of left ventricular relaxation and left atrial pressure in the left ventricular filling velocity profile.

To evaluate the determinants of left ventricular filling, left ventricular filling velocity was measured by pulsed Doppler flowmetry during catheterization of the right and left sides of the heart in 37 patients with cardiac disease before and during leg elevation. During leg elevation, despite no significant change in the time constant of isovolumic relaxation (T), the peak rapid filling velocity (PVRF) increased in association with an increase in pulmonary wedge pressure (PWP), but the peak atrial filling velocity was unchanged. The PVRF correlated with the pulmonary wedge V wave - left ventricular minimum pressure difference (r = 0.68) and in multivariate regression with both T and mean PWP (R = 0.73). These results indicate that left ventricular filling is determined by both left ventricular relaxation and left atrial pressure and that an increase in left atrial pressure changes the left ventricular filling velocity profile in a manner that mimics the pattern with normal diastolic function.

Adult↗
PubMed1989

Pharmacological properties of tiropramide, an antispasmodic drug.

1. The pharmacological properties of an antispasmodic drug, tiropramide, were studied in isolated smooth muscle preparations. 2. Tiropramide at concentrations of 10(-6) to 10(-4) M relaxed various smooth muscles contracted spontaneously and by smooth muscle stimulants or electrical stimulation. Tiropramide did not interact with all drug-receptors examined, suggesting a pure musculotropic smooth muscle relaxant activity. 3. Tiropramide was found to inhibit both Ca uptake and Ca release in the guinea pig urinary bladder. 4. Tiropramide is considered to be useful to inhibit the contractile response of the urinary bladder, as this organ is mainly innervated by noncholinergic excitatory neurons.

Animals↗
PubMed1989

Accuracy of cardiac output measured by continuous wave Doppler echocardiography during dynamic exercise testing in the supine position in patients with coronary artery disease.

To estimate the accuracy of cardiac output measured by continuous wave Doppler echocardiography from the suprasternal notch and the utility of this method for evaluating left ventricular function during dynamic exercise, simultaneous thermodilution and Doppler cardiac output were measured in 34 patients with coronary artery disease during multistage ergometer exercise in the supine position. Cardiac output was measured at rest and during each stage of exercise. Twenty-five of the 34 patients whose thermodilution curves were adequate for analysis were studied during exercise. The correlation coefficient for the two methods was 0.85 at rest and 0.84 during exercise. Differences between the two methods were not significant at rest but were significant during exercise, with the thermodilution method giving the higher values. Underestimation by the Doppler method is probably due to technical problems and changes in aortic diameter during exercise. The 25 patients were classified into two groups according to pulmonary artery wedge pressure at peak exercise. There were 11 patients in Group 1 pressure (greater than or equal to 20 mm Hg at peak exercise) and 14 in Group 2 pressure (less than 20 mm Hg at peak exercise). There were significant differences in the change in cardiac index and in peak aortic velocity from rest to peak exercise between the two groups. A significant linear correlation between the percent change in peak aortic velocity and in pulmonary artery wedge pressure from rest to peak exercise was observed (r = -0.66, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cerebral ischemia in spontaneously hypertensive rats with type 2 (noninsulin-dependent) diabetes mellitus, cerebral blood flow and tissue metabolism.

The present study was designed to examine the effect of chronic type 2 (noninsulin-dependent) diabetes mellitus on cerebral blood flow and metabolism during cerebral ischemia induced by bilateral carotid artery occlusion in spontaneously hypertensive rats. Diabetes was produced by streptozotocin treatment in 2-day neonates and the experiment was performed at the age of 5 months. The level of mean arterial pressure was not different between diabetic and nondiabetic rats. At 1 h after ischemia, cerebral blood flow was decreased to 1% of the resting value and supratentorial lactate was increased by 8-fold of control, being virtually the same in both groups of rats. In contrast, reduction of cerebral ATP was much less in diabetic rats (1.64 +/- 0.15 mmol/kg) than in nondiabetic rats (0.74 +/- 0.07 mmol/kg) (p less than 0.001); ATP in nonischemic control is 2.80-2.85 mmol/kg. These results could not be explained by the difference in cerebral blood flow between the groups during ischemia. The results suggest that chronic mild hyperglycemia exerts rather a protective effect on the brain against ischemic insult. Effective utilization of metabolites, such as glucose and ketone bodies, may play an important role to minimize metabolic derangements in the ischemic brain in type 2 diabetic-hyperglycemic rats.

Adenosine Triphosphate↗
PubMed1989

Liver, kidney and islet cell tumors in spontaneously hypertensive and normotensive rats treated neonatally with streptozotocin.

We studied the oncogenic action of neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 12 months. Two-day-old male neonates were intraperitoneally injected with STZ of which doses were 37.5-75.0 mg/kg for SHR and 100.0-150.0 mg/kg for WKY. The 12-month survival rate was 16 of 22 (73%) in SHR and 10 of 14 (71%) in WKY, respectively. The incidence of tumors in STZ-treated SHR was 27% in liver, 14% in kidney and 5% in liver and kidney, being related to the dose of STZ given, namely, 25% in 37.5 mg/kg, 50% in 50.0 or 62.5 mg/kg and 75% in 75.0 mg/kg. In STZ-treated WKY which survived 12 months, all had tumors, namely, 70% in liver, 20% in kidney and 10% in liver and kidney. Histological features of liver and kidney tumors were characteristic of hepatoma and nephroblastoma, respectively. Islet cell tumor was evident in 4 of 10 (40%) in SHR treated with lower doses of STZ (less than or equal to 50 mg/kg) but not in SHR and WKY treated with higher doses (62.5-150.0 mg/kg). The present study indicates that neonatal STZ treatment has the oncogenic action on liver, kidney and pancreatic islet.

Animals↗
PubMed1989

Morphometrical and biochemical differences of endocrine pancreata between spontaneously hypertensive and normotensive rats with or without neonatal streptozotocin-induced diabetes.

We studied the morphometrical and biochemical changes of endocrine pancreata in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) with or without noninsulin-dependent diabetes mellitus induced by neonatal streptozotocin (STZ) treatment at 4 months of age. Female (2-day-old) neonates were intraperitoneally injected with 62.5 or 75.0 mg/kg of STZ for SHR, 87.5 or 100.0 mg/kg of STZ for WKY, and vehicle for control. In STZ-treated groups, overt hyperglycemia developed in SHR with significantly decreased serum immunoreactive insulin (IRI), whereas in WKY, hyperglycemia was very mild and serum IRI was not lowered. The number and mean size of pancreatic islets did not differ between SHR and WKY, although mean islet size was reduced by half in both compared with that in the corresponding control, respectively. Percentage distribution of insulin-positive B cells in the islet was significantly reduced more in SHR than in WKY (34% of control versus 64% of control, p less than 0.05). Furthermore, pancreatic IRI content was far more reduced in SHR than in WKY (3% of control versus 43% of control, p less than 0.001). In vehicle-treated groups, the glycemic levels and the morphometrical islets did not differ between SHR and WKY. However, serum IRI was significantly lower but pancreatic IRI content was higher in SHR than in WKY. The mechanisms of strain differences between SHR and WKY seen in the present study were discussed.

Animals↗
PubMed1989

[Early recognition of exercise-induced myocardial ischemia by plasma free fatty acid].

To investigate whether or not myocardial free fatty acid (FFA) uptake is useful for early recognition of exercise-induced myocardial ischemia compared with myocardial lactate uptake, we studied in 8 patients with stable effort angina pectoris by measuring hemodynamic and metabolic parameters during supine multistage bicycle ergometer exercise (BEx). Analysis of FFA composition was performed by high performance liquid chromatography. The exercise endpoint in the control study was moderate chest pain in all cases. In all cases, BEx testing using the same method, duration and workload was repeated 1.5 hours after the oral administration of 6 mg of nilvadipine (a new calcium antagonist). Exercise time of the subjects studied was 463 +/- 40 sec (mean +/- SE, 180-540 sec). After administration of nilvadipine, chest pain was not induced in 6 patients and was lessened in severity in 2 patients. Mean ST segment depression was 0.21 +/- 0.05 mV in the control period and it was significantly reduced to 0.08 +/- 0.03 mV after nilvadipine administration (p less than 0.05). Myocardial FFA uptake decreased from 21.1 +/- 4.4% at rest to 8.1 +/- 2.1% at peak exercise in the control study (p less than 0.05). Myocardial lactate uptake was unchanged at rest and peak exercise in the control study (21.6 +/- 2.7 vs 22.2 +/- 3.3%). After administration of nilvadipine, myocardial FFA uptake did not change during BEx (25.3 +/- 2.7 at rest and 21.3 +/- 3.6% at peak exercise). At peak exercise, myocardial FFA uptake increased significantly after administration of nilvadipine (21.3 +/- 3.6 vs 8.1 +/- 2.1%, p less than 0.05). In FFA composition, the percentage of each of 12 FFA did not change during myocardial passage at rest and peak exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Thyrotropin-releasing hormone-like immunoreactive neurons in rabbit medulla oblongata.

Thyrotropin-releasing hormone-like immunoreactive (TRH-LI) neuronal cell bodies and processes were identified by using the peroxidase-antiperoxidase method in the medullar oblongata of rabbits. TRH-LI cell bodies were mainly distributed in the ventral medulla (paraolivary and parapyramidal regions), and caudal raphe nuclei (nucleus raphe obscurus and nucleus raphe pallidus). TRH-LI processes with varicosities were densely distributed in the solitary nucleus, dorsal motor nucleus of the vagus nerve and area postrema. TRH-LI processes appeared to be in contact with unlabelled cell bodies in the dorsal motor nucleus of the vagus nerve.

Animals↗
PubMed1988

Two different types of apnea induced by focal cold block of ventral medulla in rabbits.

The respiratory effects of unilateral focal cold block of ventral medulla were examined in rabbits. Focal cooling of the paraolivar region in the caudal area of ventral medulla induced prolongation of the expiratory time, with little change in the tidal inspiratory activity amplitude, leading to 'temporal apnea'. Whereas focal cooling of the region ventral to the retrofacial nucleus in the rostral part of the ventral medulla induced depression of tidal phrenic nerve activity amplitude, leading to 'suppression apnea'. Thus, two different types and regions of apnea were demonstrated in rabbits.

Animals↗
PubMed1988

Early development of nephropathy in a new model of spontaneously hypertensive rat with non-insulin-dependent diabetes mellitus.

We designed the present study to clarify whether the development of nephropathy was accelerated by a combination of hypertension and non-insulin-dependent diabetes. Spontaneously hypertensive rats with non-insulin-dependent diabetes induced by neonatal streptozotocin treatment (25.0-75.0 mg/kg) were separated into severely or mildly diabetic groups according to their non-fasting plasma glucose levels at 12 weeks of age and the findings were compared with the data on a control group treated with citrate buffer alone. The natural courses of urinary excretion rate of total protein, the molecular composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis with laser densitometer and N-acetyl-beta-D-glucosaminidase were measured in the three groups from 12 weeks until 36 weeks of age. Total urinary protein in the control group decreased with age (p less than 0.05), while in the mildly diabetic group changes were nil; in the severely diabetic group, however, the excretion rates of total urinary protein and high molecular weight protein consistently and progressively increased with age (p less than 0.05). The low molecular weight protein continuously decreased with age in the mildly diabetic and control groups (p less than 0.05), while in the severely diabetic group there was no decrease after 28 weeks of age. The urinary N-acetyl-beta-D-glucosaminidase markedly increased (p less than 0.05) in the severely diabetic group throughout the period compared with findings in the control group, but drastically decreased (p less than 0.05) in the mildly diabetic group with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗