Biomedical subjects

S Isoyama

Publications and source records attributed to S Isoyama.

At least 55 records · Page 3Linked to original sources

PubMed1991

Effects of age on right ventricular hypertrophic response to pressure-overload in rats.

To examine the effects of age on hypertrophic response to pressure-overload in the right ventricle, we determined the rate and extent of hypertrophy in three age groups of Wistar rats: 2, 7 and 18 months. We created pulmonary artery constriction so that increases in right ventricular pressure were similar in those groups. One or 3 weeks after pulmonary artery constriction, the rats were sacrificed and hypertrophic response was estimated from right ventricular weight, myocyte width and protein content. In the 2-month-old rats, significant hypertrophy was observed 1 and 3 weeks after pulmonary artery constriction in terms of right ventricular weight/body weight (161% of controls at 1 week and 209% at 3 weeks), right ventricular weight/tibial length (161 and 251%, respectively) and right ventricular weight/left ventricular weight (174 and 211%, respectively). In the 7-month-old rats, significant hypertrophy was observed only at 3 weeks, but was not observed even at 3 weeks in the 18-month-old rats. The age-associated decrease and delay in hypertrophic response was also observed at cellular (myocyte width) and biochemical (protein content) levels. Thus, there is an age-associated diminution in the rate and extent of myocardial hypertrophy in the right ventricle.

Aging↗

PubMed1991

Effect of age on coronary circulation after imposition of pressure-overload in rats.

We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy.

Aging↗

PubMed1990

Duration of pressure overload alters regression of coronary circulation abnormalities.

Using a rat model of ascending aortic banding and debanding, we examined how the duration of pressure overload affects reversibility in coronary circulation abnormalities after relief of pressure overload. Four-week banding increased left ventricular dry weight-to-body weight ratio to 158 +/- 8% of that of sham-operated controls. In isolated nonworking hearts perfused with crystalloid solution, peak mean coronary flow rate (CFR) was measured after brief ischemia. CFR and CFR/dry tissue weight significantly decreased (75 +/- 5 and 54 +/- 3% of that of controls at 100 mmHg of coronary perfusion pressure; 75 +/- 5 and 54 +/- 4% at 150 mmHg, respectively). Four weeks after debanding was performed, CFR and CFR/dry tissue weight increased to similar levels in controls. On the other hand, 10-wk banding produced the same degree of myocardial hypertrophy and decreases in CFR and CFR/dry tissue weight as in 4-wk banded rats. Four weeks after debanding was performed, CFR had not changed. CFR/dry tissue weight increased because of regression of myocardial hypertrophy but was significantly lower than that in rats debanded after 4 wk of banding. Thus the duration of pressure overload does not affect the degree of coronary circulation abnormalities in the progression process but does affect it in the regression process.

Animals↗

PubMed1990

Normalization of impaired coronary circulation in hypertrophied rat hearts.

We tested the hypothesis that impaired coronary autoregulation, decreased flow reserve, and diminished reactive hyperemic response in hypertrophied hearts with coronary arterial hypertension may be reversible after relief of pressure overload. In 4-week ascending aortic banded rats, in vivo peak systolic left ventricular pressure increased to 178 +/- 8 mm Hg (103 +/- 6 mm Hg in sham-operated control group). This increased pressure produced myocardial hypertrophy, and the left ventricular weight/body weight ratio was 46% above that of the control group. After the rats were killed, the coronary perfusion pressure-flow relations were obtained during resting conditions and maximal vasodilation after a 40-second period of ischemia in beating but nonworking isolated hearts perfused with Tyrode's solution with bovine red blood cells and albumin. In hearts from control rats, coronary autoregulation (i.e., a slight decrease in flow with reduction of pressure) was observed in the range of 50-100 mm Hg of perfusion pressure. A pronounced reactive hyperemic response was observed: a peak flow/resting flow ratio of 2.9 +/- 0.1 and a repayment ratio of 1.7 +/- 0.2 at 100 mm Hg of perfusion pressure. In hearts of banded rats the resting pressure-flow relation was rectilinear in the range of 25-175 mm Hg of perfusion pressure. Flow reserve and the time of reactive hyperemia to one half peak flow decreased at 50, 100, and 150 mm Hg of perfusion pressure compared with values in control rat hearts. Four weeks after debanding, peak systolic left ventricular pressure and cardiac hypertrophy had normalized. The impaired autoregulation, decreased flow reserve, and diminished reactive hyperemic response had completely reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Relationship between asthma and seasonal allergic rhinitis in schoolchildren.

The relationship between sensitization to common allergens and the development of asthma and seasonal allergic rhinitis (SAR) was investigated in a total of 419 schoolchildren in a farming community where allergens of both Dermatophagoides farinae (Df) and orchard grass (OG) pollen predominate. Twelve subjects (2.9%) were found to have asthma and 35 subjects (8.4%) SAR. There was no significant association between occurrences of asthma and SAR. The incidence of asthma correlated with DF-specific IgE levels but not with OG-specific IgE levels, whereas that of SAR correlated with OG-specific IgE levels but not with Df-specific IgE levels. No significant correlation was detected between IgE antibody levels against Df and OG. These results suggest that asthma occurs independently of SAR.

Adolescent↗

PubMed1989

Effects of afterload elevation on the ischemic myocardium in isolated, paced canine heart with partial coronary stenosis.

The effect of afterload elevation on the ischemic myocardium was examined in an isolated, paced canine heart with a partial coronary stenosis. The coronary blood flow of the left circumflex coronary artery was reduced to approximately one-third of the values before stenosis. The left circumflex coronary stenosis produced a decrease in global ventricular function, a decrease in systolic shortening and deviation of the ST-segment of the epicardial electrocardiogram and an increase in myocardial carbon dioxide (CO2) tension of the ischemic region. Then, afterload elevation with constant preload decreased the myocardial CO2 tension and improved the ST-segment deviation of the ischemic myocardium. Mechanical function, estimated by the relation between mean aortic pressure and systolic shortening, also improved with elevation of mean aortic pressure. In contrast, afterload elevation combined with preload elevation did not improve ischemic injury, as estimated by myocardial CO2 tension, and did not improve ST-segment deviation or mechanical function despite an increase in left circumflex coronary flow. These results suggest that the elevation of afterload pressure under constant preload improves ischemia produced by a partial coronary stenosis due to increased coronary blood supply; however, the preload elevation counterbalances the beneficial effects of afterload elevation.

Animals↗

PubMed1989

Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

Using an experimental model of ascending aortic banding in the rat, we examined whether coronary circulation abnormalities in hypertrophied hearts are reversible after debanding. 4-wk banding produced significant increases in in vivo left ventricular (LV) pressure (194 +/- 13 vs. 114 +/- 9 mmHg in shamoperated controls) and LV dry wt/body wt (48 +/- 5% above controls). In isolated hearts perfused with Krebs-Henseleit buffer, coronary flow rate (CFR) was estimated under nonworking conditions. During maximal vasodilation after 1 min-ischemia, CFR at a coronary perfusion pressure (CPP) of 100 mmHg and CFR/myocardidial mass at CPPs of 100 and 150 mmHg decreased significantly (72 +/- 5%; 53 +/- 4 and 61 +/- 4% of controls). 1 or 4 wk after debanding, LV systolic pressures were similar to control values, and the degree of myocardial hypertrophy decreased to levels 23 +/- 6 (P less than 0.01) and 11 +/- 6% (P less than 0.01) above their control values, respectively. At 1 wk there was no significant increase in CFR/myocardial mass, compared to values in the banded group (67 +/- 8 vs. 53 +/- 4% of controls at 100 mmHg and 67 +/- 9 vs. 61 +/- 4% at 150 mmHg of CPP). At 4 wk, CFR and the ratio had increased toward normal. Thus, decreased coronary perfusion in hypertrophied hearts is completely reversible.

Animals↗

PubMed1989

Contrast effects of isoproterenol and ouabain on left ventricular diastolic relaxation dysfunction in isolated, blood-perfused rabbit hearts.

We studied the influence of inotropic agents on prompt and transient left ventricular (LV) diastolic relaxation dysfunction produced by superimposition of pacing tachycardia on low-flow ischemia, using an isolated, blood-perfused and isovolumic (balloon-in-LV) rabbit heart preparation. The LV balloon volume was adjusted to produce an LV end-diastolic pressure (EDP) of 15 mmHg and was held constant thereafter. Coronary perfusion pressure was adjusted to 100 mmHg during baseline and to 20 mmHg during low-flow ischemia of 6 min. At baseline, isoproterenol and ouabain were administered to cause moderate and similar rises (14 +/- 3 and 16 +/- 4% above baseline values, respectively) in maximum + dp/dt of LVP with no change in LVEDP. In control hearts which received no drug, superimposition of 5-min pacing tachycardia on low-flow ischemia produced a significant and transient increase in LVEDP under constant LV volume (from 13.4 +/- 0.4 to 24.7 +/- 3.3 mmHg, p less than 0.01). In the hearts which received isoproterenol it did not change LVEDP (from 14.0 +/- 0.4 to 16.2 +/- 1.0 mmHg, NS). In contrast, the ouabain hearts showed a further increase in LVEDP (from 13.7 +/- 0.8 to 29.9 +/- 4.6 mmHg, p less than 0.01). LV developed pressure, myocardial oxygen consumption or myocardial lactate production during pacing tachycardia superimposed on the low-flow ischemia did not differ significantly among the 3 groups. Thus, isoproterenol markedly improved transient LV relaxation dysfunction produced by superimposition of pacing tachycardia on low-flow ischemia, in which an equipotent inotropic dose of ouabain exaggerated the relaxation dysfunction. These results suggest that calcium overload rather than ATP depletion per se contributes to transiently impaired diastolic relaxation by pacing tachycardia and low-flow ischemia.

Animals↗

PubMed1988

Effects of ouabain and isoproterenol on left ventricular diastolic function during low-flow ischemia in isolated, blood-perfused rabbit hearts.

Myocardial ischemia causes both systolic and diastolic dysfunction. A variety of positive inotropic agents with different subcellular mechanisms may be used clinically in an attempt to reverse ischemic contractile failure. We tested the hypothesis that two inotropic agents, isoproterenol (a beta-adrenergic agonist) and ouabain (a sodium pump inhibitor), might have different effects on left ventricular (LV) diastolic function during ischemic failure despite an equivalent inotropic effect. Isolated isovolumic (balloon-in-LV) blood perfused rabbit hearts were paced at constant physiological heart rate (4 Hz), given either no drug (controls, n = 7), isoproterenol (n = 7), or ouabain (n = 7), and then subjected to 6 minutes of low flow ischemia (75% reduction of baseline coronary flow). The doses of isoproterenol and ouabain were selected to produce equivalent modest inotropic effects (15% increase in LV + dP/dt) in each heart during baseline perfusion conditions. During the ischemic period, there was a marked decrease in contractility, and neither isoproterenol nor ouabain demonstrated a positive inotropic effect relative to the control group. However, these agents had markedly different effects on diastolic chamber distensibility (assessed by end-diastolic pressure at constant LV volume) during ischemia. In the control and isoproterenol groups, diastolic chamber distensibility did not change during the ischemic period. In contrast, ouabain treatment resulted in a marked decrease in diastolic chamber distensibility during ischemia; this change was not completely reversible during the 10-minute reperfusion period. The mechanism by which ouabain decreased diastolic chamber distensibility relative to isoproterenol was assessed indirectly. The ouabain and isoproterenol groups were subjected to equivalent degrees of ischemia as assessed by oxygen supply/demand imbalance; during ischemia, each drug group did not differ with regard to myocardial perfusion rates, determinants of myocardial oxygen demand (heart rate, LV developed pressure, LV + dP/dt), myocardial oxygen consumption, lactate production, and ATP and creatine phosphate content. We therefore inferred that the greater decrease in diastolic distensibility in the ouabain group was not due to a greater metabolic severity of ischemia. These observations are consistent with a mechanism of cytosolic calcium overload induced by ouabain, resulting in persistent active myofilament tension development throughout diastole, to cause the observed decrease in diastolic chamber distensibility during ischemia in the ouabain group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Effect of age on myocardial adaptation to volume overload in the rat.

To test the hypothesis that the capacity for left ventricular (LV) adaptation to volume overload might diminish with age, we examined the hemodynamics and degree of myocardial hypertrophy in response to aortic insufficiency in young adult (9 mo) and old (18 or 22 mo) Fischer rats. Before, immediately after, and at 2 and 4 wk after creating aortic insufficiency, LV and aortic pressures were measured using a catheterization technique. 4 wk after surgery, we measured aortic flow, and estimated the LV passive pressure-volume relationship and the degree of LV hypertrophy after killing. Immediately after the surgical creation of aortic insufficiency, both young and old rats showed similar elevation of LV end-diastolic pressure (from 4.8 +/- 0.6 to 12.0 +/- 1.5 mmHg in the young rats, P less than 0.01; from 4.9 +/- 0.4 to 11.0 +/- 0.7 mmHg in the old rats, P less than 0.01). In the young rats LV, end-diastolic pressure decreased to 8.0 +/- 1.0 and to 8.5 +/- 0.9 mmHg at 2 and 4 wk (P less than 0.05). In contrast, LV end-diastolic pressure at 2 (16.9 +/- 3.1 mmHg) and 4 wk (16.1 +/- 2.7 mmHg) in the old rats was even higher, compared with the values measured immediately after aortic insufficiency. At 4 wk, LV end-diastolic meridional wall stress (calculated from the in vivo LV end-diastolic pressure, and the pressure-volume relationship and muscle mass obtained after killing) was higher in the old rats than in the young rats. In the young rats, the diastolic pressure-volume relationship at 4 wk shifted to the right (P less than 0.01), and LV dry weight, LV dry weight/tibial length, and protein content of the LV myocardium increased by 26% (P less than 0.01), 24% (P less than 0.01), and 33% (P less than 0.01), respectively. However, old rats with aortic insufficiency did not show a significant change in the pressure-volume relationship, dry weight, or protein content at 4 wk. These results suggest that advanced age diminishes the capacity for LV hypertrophy in response to a volume overload, and this reduced LV hypertrophic response in the old rats resulted in persistent elevation of LV end-diastolic pressure and wall stress.

Adaptation, Physiological↗

PubMed1988

Load dependency of end-systolic pressure-volume relations in isolated, ejecting canine hearts.

If characteristic muscle properties such as myocardial viscosity and/or shortening deactivation influence left ventricular ejection in the whole heart, the slope of the left ventricular end-systolic pressure-volume relation should be a function of both the contractile state and the loading mode. Thus, the load dependence of the end-systolic pressure-volume relation was examined using isolated, perfused canine hearts ejecting saline into a hydraulic loading system. The instantaneous left ventricular volume was measured with a plethysmograph. Under constant coronary flow and heart rate, two regression lines for end-systolic pressure-volume relations in two sets of loading modes were obtained: (1) Preload (left ventricular end-diastolic pressure; 4-15 mmHg) changes under fixed afterload impedance (preload changes); (2) Afterload impedance (peripheral resistance; 1.9-9.6 x 10(3) dyn sec cm-5) changes under fixed left ventricular end-diastolic volume (afterload changes). The slope of the end-systolic pressure-volume relation with afterload changes was steeper than that with preload changes (6.3 +/- 0.7 vs 4.8 +/- 0.6 mmHg/ml, p less than 0.05). Accordingly, under constant coronary flow, the slope of the end-systolic pressure-volume relation depended on loading conditions within the physiological range of afterload impedance and preload. This finding supports our hypothesis and implies that the slope change is of limited value as a contractile index in the ejecting heart.

Animals↗

PubMed1987

Effects of changes in afterload impedance on left ventricular ejection in isolated canine hearts: dissociation of end ejection from end systole.

To examine how end systole differs from end ejection and also whether the slope of the end systolic pressure-volume relation can be approximated to that of the end ejection pressure-volume relation, nine isolated, perfused, paced canine hearts ejecting into a hydraulic loading system that simulated the aortic input impedance of a dog's arterial tree were studied. To measure left ventricular volume changes the heart was placed in a plethysmograph. Peripheral resistance (Rp) and arterial compliance (C) were independently varied from 1.9 (Rp = 1.9) to 3.3, 6.4, and 9.6 X 10(8) Pa.m-3.s (Rp run) with a constant value of compliance 1.3 X 10(-9) Pa-1.m3 (C = 1.3), and from C = 0.4 to C = 0.8, C = 1.3 and C = 2.3 (C run) with a constant value of resistance (Rp = 6.4). Five pressure-volume loops were obtained by changing the end diastolic volume at each value of compliance and peripheral resistance. It was clearly shown that ventricular ejection continued after end systole and the time duration between end systole and end ejection became longer with increasing arterial compliance (24(4) at C = 0.4 vs 49(4) ms at C = 2.3, p less than 0.001), while the time duration between end diastole and end systole was constant regardless of afterload impedance change. Regarding the left ventricular pressure-volume relation the end systolic relation was almost linear (r greater than or equal to 0.98) and the slope was not significantly affected by change in any afterload impedance tested. End ejection pressure-volume relation was also linear (r greater than or equal to 0.97) and the slopes in the peripheral resistance and compliance runs were lower than those of the end systolic pressure-volume relation in each corresponding run. The former slopes decreased at smaller values of Rp or larger values of C--namely, 4.4(0.6) at Rp = 9.6 vs 3.6(0.6) at Rp = 1.9, p less than 0.05; 4.8(0.6) at C = 0.4 vs 3.1(0.5) mmHg.ml-1 at C = 2.3, p less than 0.001. Thus it is concluded that end ejection is usually different from end systole and the time difference between them is affected by changes in arterial compliance. In addition, the slope of end ejection pressure-volume relation was dependent on the changes in afterload impedance and cannot be approximated to that of the end systolic pressure-volume relation.

Animals↗

PubMed1987

Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat.

To test the hypothesis that the capacity to develop left ventricular (LV) hypertrophy might diminish with advancing age, we examined the hypertrophic response to ascending aortic constriction in 3 groups of adult Fischer 344 rats (9 months, 18 months, and 22 months of age). Aortic constriction was created so that aortic cross-sectional areas would be the same for the 3 groups of rats. Four weeks after imposition of aortic constriction, there was no significant difference in peak LV pressure, peak-to-peak and mean systolic pressure gradients between left ventricle and aorta, cardiac output, LV minute work, or cross-sectional area of the aortic constrictions in the 3 groups. In 9-month-old aortic-constricted rats, LV dry wt (LVDW)/body wt, LVDW/tibial length, and myocyte width increased by 23% (p less than 0.01), 14% (p less than 0.01), and 27% (p less than 0.01), respectively, compared with sham-operated rats. In contrast, in 18-month-old and 22-month-old aortic-constricted rats, LVDW/body wt and LVDW/tibial length were unchanged compared with sham-operated controls, and increases in myocyte width were only modest 4 weeks following constriction. RNA concentration in the myocardium 5 days after constriction increased by 21% (p less than 0.001) in 9-month-old rats but showed no significant rise in 18-month-old rats. These results suggest that advancing age is associated with a diminished capacity to develop myocardial hypertrophy in response to acute pressure overload and that a reduced ability to synthesize protein may be one of the major contributing factors to a diminished capacity for hypertrophy in advanced age.

Aging↗

PubMed1987

Acute decrease in left ventricular diastolic chamber distensibility during simulated angina in isolated hearts.

It is not clear what factors contribute to the prompt and reversible decrease in left ventricular diastolic chamber distensibility during angina pectoris that is induced by an increase in myocardial energy demand due to exercise or pacing tachycardia. To simulate the demand ischemia that occurs clinically during pacing-induced angina, we used isolated, blood-perfused rabbit hearts with restricted coronary flow and increased myocardial energy demand. A constant left ventricular balloon volume model was used to measure left ventricular diastolic chamber distensibility during 6 minutes of low-flow global ischemia, induced by a reduction in coronary perfusion pressure from 100 to 20 mm Hg. To investigate the influence of different levels of myocardial energy demand, the effects of two different heart rates were studied during low-flow global ischemia; pacing tachycardia (6.4 +/- 0.2 Hz, n = 7) was compared with the rabbit's baseline heart rate of 4 Hz (n = 7). Low-flow ischemia caused a marked decrease in contractile function relative to the baseline preischemic state. In the pacing-tachycardia group, myocardial energy demand, as estimated by the rate X systolic pressure product, was significantly greater than in the constant heart-rate group. When tachycardia was imposed during low-flow global ischemia, there was a transient and reversible increase in isovolumic left ventricular end-diastolic pressure from 14 +/- 1 to 25 +/- 4 mm Hg (measured during long diastoles obtained with transient cessation of pacing) in the pacing-tachycardia group, but there was no increase in left ventricular end-diastolic pressure during low flow ischemia in the constant heart-rate group with lower energy demand (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1986

Measurement of instantaneous viscoelastic properties by impedance-frequency curve of the ventricle.

We developed a method for estimating the instantaneous viscoelastic properties of the left ventricle (LV). This impedance-curve method is based on the instantaneous impedance-frequency curve of the left ventricle generated by a rapidly oscillating mechanical impulse applied to the epicardial surface of the heart. The theoretical basis of the method and experimentally obtained instantaneous impedance-frequency curves were examined to evaluate the validity of our basic assumptions. Using these impedance-curve data, we calculated the instantaneous viscoelastic properties of the LV during the cardiac cycle. The impedance curve shows a configuration that is almost the same as the theoretical curve based on the assumption that an RCL (R, resistor; C, capacitor; L, inductor) parallel circuit is the electrical analog for the LV. The impedance curve varied moment by moment during the development of instantaneous LV pressure. The elastic and viscous coefficients, calculated from the impedance curve, increased with increase of LV pressure. We concluded that the impedance-curve method can delineate the instantaneous viscoelastic properties of the ventricle (especially of the ventricular myocardium).

Animals↗

PubMed1986

Effects of preload alteration on the degree of ischemia and function of ischemic myocardium under constant mean aortic pressure, coronary perfusion pressure and heart rate in isolated perfused canine heart.

We examined the effects of preload alteration on global and regional (i.e., non-ischemic and ischemic areas) function in the presence of regional myocardial ischemia and on the degree of ischemia using 18 isolated, metabolically supported canine left ventricles. For this purpose, cardiac output (CO), systolic segment length change (SL), myocardial CO2 tension (PmCO2) and ST level of epicardial ECG were measured at 3 levels of left ventricular end-diastolic pressure (LVEDP), i.e., approximately 7 (low LVEDP), 11 (middle LVEDP), and 16 mmHg (high LVEDP) without and with left circumflex artery (LCx) stenosis under a constant mean aortic pressure (90 mmHg), mean coronary perfusion pressure (90 mmHg) and heart rate. In the Pre-ischemic stage, CO and SL increased significantly when LVEDP was elevated in a stepwise fashion by changing the height of the reservoir connected to the left atrium. There were no significant changes in PmCO2 or ST level. On the other hand, with LCx stenosis, CO did not show a subsequent increase at higher LVEDPs (i.e., from 796 +/- 103 ml/min at middle LVEDP to 931 +/- 153 ml/min at high LVEDP). Furthermore, there was no significant SL response in the LCx area following alterations of LVEDP, although there was considerable lengthening of end-diastolic length. Both increased PmCO2 and ST level of the LCx area, following LCx stenosis, further increased significantly with elevation of LVEDP. These results suggest the possibility that considerable elevation of LVEDP worsens the degree of ischemia and does not significantly augment ischemic regional myocardial function or global function, while mild elevation of preload improves or tends to improve simultaneously regional ischemic and global functions without aggravating the ischemic injury significantly. Therefore, we conclude that the preload level is quite important in managing ischemia induced myocardial dysfunction.

Animals↗

PubMed1986

The changes in ECG ST segment and mechanical function of regional ischemic myocardium during afterload reduction in isolated dog hearts with coronary stenosis.

By measuring ECG ST segment deviation and regional mechanical dysfunction, we assessed the effects of an alteration in afterload pressure on regional myocardial ischemia due to a partial coronary occlusion of the left circumflex coronary artery (CFX). Eight isolated, perfused and paced dog hearts were loaded with an artificial arterial system which simulated the aortic input impedance of the dog arterial tree. Afterload pressure was altered by stepwise changes in peripheral resistance (Rp), while left ventricular end-diastolic pressure (LVEDP) and heart rate were kept constant. Coronary perfusion pressure (CPP) was kept equal to mean aortic pressure (AoP). ECG and myocardial systolic segment shortening (SS) were measured in both areas perfused by the CFX and the left anterior descending coronary artery (LAD). In the presence of CFX stenosis, mean AoP decreased from 96 +/- 7 to 46 +/- 7 mmHg following a decrease in Rp and cardiac output increased progressively from 465 +/- 30 to 1055 +/- 100 ml/min. In this situation, CFX coronary blood flow decreased from 75 +/- 2 to 28 +/- 6 ml/100 g/min. Epicardial ECG in the ischemic region showed two types of ST segment deviation after CFX stenosis: ST segment elevation and ST segment depression. Moreover, following afterload reduction, these individual ECG ST segment changes showed further deviations. The levels of mean AoP, below which further ST segment deviations significantly occurred, were as follows: 71 +/- 6 mmHg in ST segment elevation cases and 52 +/- 7 mmHg in ST segment depression cases. Myocardial systolic segment shortening in the ischemic region also significantly decreased following CFX stenosis (91 +/- 8% of pre-ischemic control, p less than 0.05). Then, during afterload reduction, SS in the CFX area appeared to be bimodal and it definitely decreased when mean AoP was 46 +/- 7 mmHg. To enhance the sensitivity of detection of further mechanical dysfunction throughout afterload reduction following regional myocardial ischemia, we calculated percentage values of the SS in the CFX area to the SS in the LAD area at each Rp. By this normalization, mechanical dysfunction was found when mean AoP was below 67 +/- 5 mmHg. These results suggest that reduction in afterload pressure below a certain level aggravated the regional ischemia, despite an increase in cardiac output, and to detect this change in the ischemic region during afterload reduction, ECG ST segment deviation seems to be a useful indicator.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Effects of major coronary artery stenosis on the pressure-flow relationship of an adjacent intact coronary artery branch in isolated supported canine left ventricle.

We investigated whether the relationship between the mean left anterior descending and septal coronary blood flow and the mean perfusion pressure varies with left circumflex coronary stenosis. We used excised, perfused canine heart preparations (n = 10), in which variables to influence the myocardial oxygen demand and supply relation can be fairly well controlled. The results showed that coronary blood flow in the adjacent, non-stenosed coronary artery increased significantly following LCX stenosis; this increased flow was found at the same values of heart rate, left ventricular end-diastolic pressure and perfusion pressure, as those in the preischemic state. Moreover, this increased flow was also observed when the values of peak left ventricular pressure and pressure-length loop area were similar between the pre-ischemic and ischemic states. Thus, contributions of neurohumoral factors or alterations in mechanical factors determining the myocardial oxygen demand and supply relation are negligible. This increased flow may be important in maintaining overall cardiac function in cases of acute coronary stenosis or coronary occlusion.

Animals↗