Biomedical subjects

S Isoyama

Publications and source records attributed to S Isoyama.

At least 19 recordsLinked to original sources

PubMed1992

Effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in rats.

The aim of this study was to determine the effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in hypertropied hearts. The experiments were performed on 38 anesthetized male Wistar rats aged 6 to 8 weeks. The ascending aorta was banded for 4 or 10 weeks, then in some rats the bands were removed for 4 weeks. We estimated coronary hemodynamics in a model consisting of isolated non-working hearts perfused with Tyrode's solution containing bovine red blood cells and serum albumin. Myocardial mass increased significantly in 4 and 10-week banded groups compared to controls. Four weeks after debanding in 4- and 10-week banded groups, the value returned to that of controls. Autoregulation gain was significantly lower in banded groups than in controls in the range between 50 and 100 mmHg of coronary perfusion pressure. Although the gain normalized in the debanded group after 4 weeks of banding, the value in the debanded groups after 10 weeks of banding remained less than zero between 25 and 150 mmHg of perfusion pressure. In transient flow response to a stepwise increase of perfusion pressure within the autoregulatory range, promptly increased flow was followed by more rapid and greater decrease in controls than in banded groups. The flow response regressed in the debanded group after 4 weeks of banding, while it remained unchanged in the debanded group after 10 weeks of banding. Thus, duration of pressure overload alters the regression of impaired coronary autoregulation in cardiac hypertrophy.

Animals↗

PubMed1992

Interaction of lectins with human IgE: IgE-binding property and histamine-releasing activity of twelve plant lectins.

We examined the IgE-binding reaction and the histamine-releasing response of basophils to a panel of 12 lectins: concanavalin A (Con A), Lens culinaris hemagglutinin (LcH), Pisum sativum agglutinin (PSA), wheat germ agglutinin (WGA), soybean agglutinin (SBA), Bauhinia purpurea agglutinin (BPA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), Lotus tetragonolobus agglutinin (Lotus A), Ulex europeus agglutinin I (UEA-I), phytohemagglutinin E (PHA-E) and phytohemagglutinin L (PHA-L), IgE from allergic patients bound with high affinity to Con A, LcH, PSA, RCA-I and PHA-E, and with lower affinity to WGA, BPA, Lotus A and UEA-I, but they did not bind to SBA, PNA or PHA-L. There was no apparent individual difference in the reactivity of IgE to these lectins between 10 IgE preparations from allergic patients. The binding to these lectins, except Lotus A and UEA-I, were competitively inhibited by the lectin-specific sugars or glycopeptide. Upon stimulation by Con A, LcH, PSA, WGA, RCA-1 and PHA-E, leukocytes from allergic patients showed a significant release of histamine, but cells from IgE-deficient subjects did not respond to these lectins. The histamine-releasing responses by these lectins were also inhibited by specific sugars or glycopeptides.

Basophils↗

PubMed1992

Collagen deposition and the reversal of coronary reserve in cardiac hypertrophy.

The aim of this study was to clarify how collagen deposition or medial hypertrophy of the vascular wall affects the coronary dilator reserve in pressure-overloaded hearts and whether inhibition of collagen deposition reverses the abnormalities after relief of pressure overload. We used ascending aortic banding and debanding methods and superimposed beta-aminopropionitrile in some of the banded rats (50 mg/kg i.p., twice a day). Ten weeks of banding increased in vivo peak systolic left ventricular pressure and produced medial hypertrophy, an increase in collagen deposition in the myocardial and perivascular tissues, and myocardial hypertrophy in the banded group without beta-aminopropionitrile treatment. Superimposition of beta-aminopropionitrile treatment on banding inhibited the increase in collagen deposition. In the groups debanded after the 10-week banding period, both with and without beta-amino-propionitrile treatment, medial and myocardial hypertrophy regressed 4 weeks after debanding. We estimated coronary dilator reserve in Langendorff preparations perfused with modified Tyrode's solution containing oxygenated bovine red blood cells and serum albumin. The ratio of reactive peak flow after brief ischemia-to-resting flow decreased in both of the banded groups. After debanding, the ratio remained lower in the banded group without beta-aminopropionitrile treatment than in the control group. However, debanding in the group with beta-aminopropionitrile treatment increased the ratio to a level similar to that of the control group. Thus, in pressure-overloaded cardiac hypertrophy with coronary hypertension, coronary reserve seems to be determined by medial hypertrophy independently of collagen deposition, but collagen deposition plays an important role in the reversal of vasodilator reserve after relief of the overload.

Aminopropionitrile↗

PubMed1992

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

Cardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression of c-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of beta- to alpha-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca(2+)-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal alpha-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac alpha-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress.

Actins↗

PubMed1992

Aging effects on myocardial hypertrophic response and coronary circulation in pressure-overload.

We examined the effect of age on capacity for myocardial hypertrophy, pressure-generating ability and coronary circulation after imposition of pressure-overload. Marked right ventricular and cellular hypertrophy was observed 1 week after pulmonary artery constriction in the developmental phase of rats (2 months of age) and after 3 weeks in the young-adult rats (7 months). In old rats (18 months) similar increases in peak right ventricular pressure did not produce significant hypertrophy even after 3 weeks. The right ventricular hypertrophy at the organ and cell levels in response to pressure-overload decreased with age. In vivo pressure-generating ability, which was determined by maximum isovolumic pressure during pulmonary artery occlusion, correlated with the degree of myocardial hypertrophy in each age group. During the ascending aortic constriction experiment the age-associated diminution in hypertrophic response was also observed in the left ventricle. Coronary dilator capacity, which was determined after brief ischemia in an isolated, blood-perfused, beating but nonworking heart model, was decreased in the presence of myocardial hypertrophy in young-adult rats (7 months) and in the absence of significant myocardial hypertrophy in old rats (18 months). The age-associated diminution in capacity for myocardial hypertrophy, pressure-generating ability and maladaptation in the coronary circulation may explain the higher incidence of heart failure or increased vulnerability of the myocardium to ischemic episodes during hemodynamic stress in aged patients.

Aging↗

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↗