Biomedical subjects

R Tian

Publications and source records attributed to R Tian.

At least 37 records · Page 2Linked to original sources

PubMed1997

Failure to maintain a low ADP concentration impairs diastolic function in hypertrophied rat hearts.

BACKGROUND: Mechanisms in addition to diastolic calcium overload may contribute to diastolic dysfunction in hypertrophied hearts. In this study, we tested the hypothesis that failure to maintain a low ADP concentration in hypertrophied hearts contributes to diastolic dysfunction by inhibiting the rate of cross-bridge cycling. METHODS AND RESULTS: By perfusing isolated rat hearts with pyruvate and 2-deoxyglucose (2DG), we were able to perturb [ADP] with minimal changes in [ATP] and [inorganic phosphate] or the contribution of glycolytic ATP to ATP synthesis. The effects of 2DG were compared in aortic-banded (LVH, n=5) and sham-operated (control, n=5) rat hearts. 31P NMR spectroscopy was used to measure the concentrations of phosphorus-containing compounds. We found a threefold increase of left ventricular end-diastolic pressure (LVEDP) in LVH during 2DG perfusion, and this increase was concomitant with a threefold increase in intracellular free [ADP]. The [ADP] in the control hearts was maintained <40 micromol/L, and no change in LVEDP was observed. A linear relationship between increases in [ADP] and LVEDP was found (r2=.66, P=.001). Furthermore, the capacity of the creatine kinase reaction, a major mechanism for maintaining a low [ADP], was decreased in LVH (P=.0001). CONCLUSIONS: Increased [ADP] contributes to diastolic dysfunction in LVH, possibly due to slowed cross-bridge cycling. Decreased capacity of the creatine kinase reaction to rephosphorylate ADP is a likely contributing mechanism to the failure to maintain a low [ADP] in LVH.

Adenosine Diphosphate↗

PubMed1997

Role of MgADP in the development of diastolic dysfunction in the intact beating rat heart.

Sarcomere relaxation depends on dissociation of actin and myosin, which is regulated by a number of factors, including intracellular [MgATP] as well as MgATP hydrolysis products [MgADP] and inorganic phosphate [Pi], pHi, and cytosolic calcium concentration ([Ca2+]c). To distinguish the contribution of MgADP from the other regulators in the development of diastolic dysfunction, we used a strategy to increase free [MgADP] without changing [MgATP], [Pi], or pHi. This was achieved by applying a low dose of iodoacetamide to selectively inhibit the creatine kinase activity in isolated perfused rat hearts. [MgATP], [MgADP], [Pi], and [H+] were determined using 31P NMR spectroscopy. The [Ca2+]c and the glycolytic rate were also measured. We observed an approximately threefold increase in left ventricular end diastolic pressure (LVEDP) and 38% increase in the time constant of pressure decay (P < 0.05) in these hearts, indicating a significant impairment of diastolic function. The increase in LVEDP was closely related to the increase in free [MgADP]. Rate of glycolysis was not changed, and [Ca2+]c increased by 16%, which cannot explain the severity of diastolic dysfunction. Thus, our data indicate that MgADP contributes significantly to diastolic dysfunction, possibly by slowing the rate of cross-bridge cycling.

Adenosine Diphosphate↗

PubMed1997

Sequence identity of the terminal redundancies on the minus-strand DNA template is necessary but not sufficient for the template switch during hepadnavirus plus-strand DNA synthesis.

The template for hepadnavirus plus-strand DNA synthesis is a terminally redundant minus-strand DNA. An intramolecular template switch during plus-strand DNA synthesis, which permits plus-strand DNA elongation, has been proposed to be facilitated by this terminal redundancy, which is 7 to 9 nucleotides long. The aim of this study was to determine whether the presence of identical copies of the redundancy on the minus-strand DNA template was necessary and/or sufficient for the template switch and at what position(s) within the redundancy the switch occurs for duck hepatitis B virus. When dinucleotide insertions were placed within the copy of the redundancy at the 3' end of the minus-strand DNA template, novel sequences were copied into plus-strand DNA. The generation of these novel sequences could be explained by complete copying of the redundancy at the 5' end of the minus-strand DNA template followed by a template switch and then extension from a mismatched 3' terminus. In a second set of experiments, it was found that when one copy of the redundancy had either three or five nucleotides replaced the template switch was inhibited. When the identical, albeit mutant, sequences were restored in both copies of the redundancy, template switching was not necessarily restored. Our results indicate that the terminal redundancy on the minus-strand DNA template is necessary but not sufficient for template switching.

Animals↗

PubMed1996

Alterations of performance and oxygen utilization in chronically infarcted rat hearts.

Progressive dilatation of left ventricle has been demonstrated in hearts post-infarction. However, the relationship of performance and energy consumption in chronically infarcted heart has not been clarified. To address this problem, we measured left ventricular pressure and oxygen consumption (MVO2) during stepwise increases in left ventricular filling volume in isolated isovolumic buffer-perfused rat hearts 8 weeks after let coronary artery ligation or sham-operation. Systolic pressure-volume area (PVA) was calculated as an estimate of total mechanical energy consumed by the heart. The MVO2-PVA relation was analysed to define the economy of the contractile machinery in surviving myocardium. Structural dilatation and reduced pressure generation in infarcted hearts were indicated by a rightward shift of pressure-volume curves and a reduced maximal developed pressure of the left ventricle (80 +/- 5 v 119 +/- 4 mmHg, P < 0.01) which was obtained at substantially higher left ventricular volume compared to control hearts (0.79 +/- 0.02 v 0.39 +/- 0.01 ml, P < 0.01). The slope of the MVO2-PVA relation was significantly lower in the infarcted compared to the control groups (1.02 +/- 0.16 v 1.44 +/- 0.10 10(-5) mlO2/mmHg/ml, P < 0.05), reflecting an increased efficiency of chemomechanical energy transduction in surviving myocardium. However, at the similar MVO2 ventricular pressure development was significantly lower in infarcted hearts due to the unfavorable geometry resulting from ventricular dilatation.

Animals↗

PubMed1996

Depletion of energy reserve via the creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters.

To study the contribution of myocardial energy reserve to the deterioration of cardiac function during the development of heart failure, we defined energy reserve via the creatine kinase (CK) reaction and the isovolumic contractile performance in hearts of cardiomyopathic hamsters at the ages of 1.5, 4, 17, 30 and 43 weeks and in age-matched normal hamsters. Energy reserve via the CK reaction was estimated by the product of total CK activity and the content of total creatine in the heart. Isovolumic contractile performance was measured as rate pressure product (RPP, 10(3) mmHg/min) in isolated hearts. Contractile reserve was assessed as the increase of RPP elicited by high calcium stimulation. Compared to the controls, decreases in total CK activity and content of total creatine were observed in hearts of 17-, 30- and 43-week-old cardiomyopathic hamsters. These changes were not observed in the skeletal muscle. Although the decrease of baseline RPP first occurred at the age of 30 weeks (11.5 +/- 0.9 v 20.5 +/- 0.8, P < 0.05), the contractile reserve was already reduced at the age of 17 weeks (9.9 +/- 1.3 v 23.6 +/- 1.9, P < 0.05). A linear relationship was found between the energy reserve via creatine kinase reaction and the contractile reserve of the heart (r2 = 0.85). Furthermore, concomitant decreases in the CK reaction velocity and the contractile reserve were observed in cardiomyopathic hearts, suggesting that depletion of energy reserve may contribute to the development of heart failure.

Age Factors↗

PubMed1996

Regional biochemical remodeling in non-infarcted tissue of rat heart post-myocardial infarction.

Changes in the capacities of ATP-synthesizing reactions were analysed in residual non-infarcted myocardium following myocardial infarction. Rats were subjected to left coronary artery ligation (MI; n = 11) or to sham operation (sham; n = 18). Two months later, hearts were excised, rinsed and buffer-perfused isovolumically. In vitro pressure-volume relationships were recorded. After separation into left and right ventricles (LV, RV) and atria (LA, RA), samples were analysed for citrate synthase, glycolytic enzymes (phosphofructokinase, glyceraldehyde-3-phosphate-dehydrogenase, lactate dehydrogenase (LDH) and its isoforms) and the creatine kinase (CK) system [total CK, CK isoenzymes (CKBB, CKMB, CKMM and CKmito) and total creatine]. In residual intact heart, citrate synthase activity and activities of most glycolytic enzymes were unchanged, but LDH activity and anaerobic LDH isoenzymes increased significantly. Total creatine kinae activity (6.5 +/- 0.2 IU/mg protein in sham LV) was decreased by chronic myocardial infarction in LV (5.4 +/- 0.3, with P < 0.05 sham v MI) but not in RV (6.2 +/- 0.2). Significant CK isoenzyme shifts occurred in both ventricles "adult" CKmito (32.5 +/- 1.4% in sham LV) was reduced in LV (22.1 +/- 2.1% with P < 0.05 sham v MI) and in RV (19.2 +/- 2.9%, with P < 0.05 sham v MI), "fetal" CKBB and CKMB increased. Total creatine content was reduced by up to 35% in both ventricles. In sham hearts atria had lower total and mitochondrial CK activity, lower total creatine content and higher CKMB and CKBB activity compared to ventricles; however, myocardial infarction induced changes directionally comparable to the changes observed in ventricles. Thus, 2 months after myocardial infarction changes of the capacities of ATP synthesizing reactions are comparable for all heart chambers, with the exception of total CK activity decreasing only in left ventricular tissue.

Animals↗

PubMed1996

Long-term beta-blocker treatment prevents chronic creatine kinase and lactate dehydrogenase system changes in rat hearts after myocardial infarction.

OBJECTIVES: We tested the hypothesis that long-term beta-blocker treatment with bisoprolol prevents creatine kinase (CK) and lactate dehydrogenase system changes that occur after chronic myocardial infarction. BACKGROUND: The mechanism of the beneficial effect of beta-blocker therapy is still unclear. METHODS: Six groups of rats were studied. Sham operated (sham) and hearts with ligated left anterior descending coronary artery (myocardial infarction) were untreated, treated early (beginning 30 min after infarction) or treated late (beginning 14 days after infarction). After 8 weeks, hearts were isolated and buffer perfused isovolumetrically. With a left ventricular balloon, mechanical function was recorded at an end-diastolic pressure of 10 mm Hg. Biopsy samples of noninfarcted left ventricular tissue were taken. Enzyme activities were measured spectrophotometrically; isoenzymes were separated by agar gel electrophoresis; and total creatine levels were measured with high performance liquid chromatography. RESULTS: The decrease in left ventricular developed pressure in untreated hearts (120 +/- 9 vs. 104 +/- 5 mm Hg [mean +/- SE], p < 0.05, sham vs. myocardial infarction) after myocardial infarction was prevented by early treatment (118 +/- 9 vs. 113 +/- 4 mm Hg). Late treatment failed to improve mechanical function. Reduction of CK activity occurring in untreated infarcted hearts (6.4 +/- 0.3 vs. 5.1 +/- 0.3 IU/mg protein, p < 0.05, sham vs. myocardial infarction) was prevented by early beta-blocker therapy. The increase in CK isoenzyme BB and MB levels, decrease in mitochondrial CK isoenzyme levels and increase in anaerobic lactate dehydrogenase isoenzyme levels in untreated infarcted hearts did not occur during bisoprolol treatment. The decrease in total creatine levels after myocardial infarction (74.2 +/- 4.9 vs. 54.9 +/- 3.3 nmol/mg protein, p < 0.05, sham vs. myocardial infarction) was prevented by bisoprolol treatment. Early treatment was more effective than late therapy in preventing CK and lactate dehydrogenase system changes. In addition, in sham hearts, a 40% increase of creatine levels above normal levels was detected. CONCLUSIONS: Bisoprolol prevented changes in CK and lactate dehydrogenase system that occur after myocardial infarction. These observations may be related to the beneficial effects of long-term beta-blocker treatment in patients with chronic myocardial infarction.

Adrenergic beta-Antagonists↗

PubMed1996

Mutations within DR2 independently reduce the amount of both minus- and plus-strand DNA synthesized during duck hepatitis B virus replication.

The initial aim of this study was to examine the role of complementarity between the plus-strand primer and the minus-strand DNA template for translocation of the plus-strand primer in hepadnaviral replication. We show that when a 5-nucleotide substitution was placed in either DR1 or DR2, translocation of the primer at a detectable level did not occur. Placing the mutation in both DR1 and DR2 did not restore primer translocation, which indicates that complementarity is not the sole determinant for primer translocation. These mutants, in which primer translocation has been inhibited, have been additionally informative. The mutation in DR1 led to efficient synthesis of plus-strand DNA, albeit primed in situ. In contrast, the mutation in DR2 resulted in a reduction in the amount of plus-strand DNA synthesized per unit of minus-strand DNA. These findings were interpreted as indicating that a mutation at DR2, the primer acceptor site, can inhibit both primer translocation and in situ priming. Lastly, we show that mutations within DR2 can result in a reduction in the synthesis of minus-strand DNA and that this reduction is occurring at an early phase of the process. We speculate that this reduction in the amount of minus-strand DNA synthesized could be due to an inhibition of the template switch during minus-strand DNA synthesis.

Animals↗

PubMed1996

Energetic basis for reduced contractile reserve in isolated rat hearts.

To study the relationship between myocardial energetics and contractile reserve, we acutely and selectively inhibited creatine kinase (CK) activity in isolated perfused rat hearts, using increasing doses of iodoacetamide. 31P nuclear magnetic resonance spectroscopy was used to measure intracellular pH and the concentrations of ATP, phosphocreatine, and inorganic phosphate. Contractile reserve was assessed as the increase of rate-pressure product (RPP) from baseline during high-calcium perfusion. Contractile reserve was reduced by 9, 35, and 72% in hearts with 26, 6, and 1% CK activity, respectively. An inverse linear relationship between RPP and the free energy release from ATP hydrolysis ([delta G approximately P[) was shown for all groups. Furthermore, the maximal RPPs of all hearts were achieved at the same level of [delta G approximately P[ (52-53 kJ/mol), which is equal to the free energy requirement of sarcoplasmic reticulum Ca2+ adenosine 5'-triphosphatase (ATPase). We suggest that inhibition of the CK reaction caused a decrease of [delta G approximately P[ which, in turn, limits the Ca(2+)-handling capacity of sarcoplasmic reticulum Ca2+ ATPase. In this way, the ability of the heart to increase its contractile performance is restricted.

Adenosine Triphosphate↗

PubMed1995

Transfer of the minus strand of DNA during hepadnavirus replication is not invariable but prefers a specific location.

The current model for replication of duck hepatitis B virus has reverse transcription initiating and copying a UUAC motif within the encapsidation signal, epsilon, near the 5' end of the RNA template. This results in synthesis of four nucleotides of DNA. This short minus-strand DNA product is then transferred to a complementary position, at DR1, near the 3' end of the RNA template. Elongation of minus-strand DNA then ensues. We have examined the transfer of minus-strand DNA during replication of duck hepatitis B virus in cell culture. The initial aim of this work was to examine the effect of mutations at DR1 on the transfer process. We found that when mutations were introduced into the UUAC motif overlapping DR1, the 5' end of minus-DNA no longer mapped to position 2537 but was shifted two or four nucleotides. Mismatches were predicted to exist at the new sites of elongation. Elongation from nucleotide 2537 could be restored in these mutants by making compensatory changes in the UUAC motif within epsilon. This finding led us to examine limitations in the shifting of the site of transfer. When the UUAC motif in epsilon was changed to six different tetranucleotide motifs surrounding position 2537, transfer of minus-strand DNA shifted predictably, albeit inefficiently. Also, when multiple UUAC motifs were introduced near DR1, the UUAC motif at nucleotide 2537 was used preferentially. Overall, our findings confirm the current minus-strand DNA transfer model and demonstrate a marked preference for the site of the transfer.

Animals↗

PubMed1995

Inhibition of the creatine kinase reaction decreases the contractile reserve of isolated rat hearts.

To define the relation between phosphoryl transfer via creatine kinase (CK) and the ability of the intact beating heart to do work, we chemically inhibited CK activity and then measured cardiac performance under physiological and acute stress conditions. Isolated perfused rat hearts were exposed to iodoacetamide (IA) and subjected to one of three cardiac stresses: hypercalcemic (Ca2+ = 3 mM) buffer perfusion (n = 7), norepinephrine (2 mumol/min) infusion (n = 6), or hypoxic buffer perfusion (n = 5). IA decreased CK activity to near zero, measured in intact hearts by 31P magnetization transfer, and to 2% of control CK activity, measured in myocardial homogenates. The CK isoenzyme profile was unchanged, suggesting nonselective IA inhibition of all isoenzymes. Mitochondria isolated from IA-treated hearts had normal ADP:O ratios, state 3 respiratory rates, and unchanged acceptor and respiratory control ratios. Neither actomyosin adenosinetriphosphatase nor adenylate kinase activities were changed. After IA exposure, end-diastolic pressure, left ventricular developed pressure, and heart rate were unchanged for at least 30 min at physiological perfusion pressures, but large changes were observed during stress conditions. The increase in left ventricular developed pressure induced by hypercalcemic perfusion and by norepinephrine infusion decreased by 39 and 54%, respectively. During hypoxia, the rate of phosphocreatine depletion was decreased by 57%, left ventricular developed pressure declined, and end-diastolic pressure increased faster than in controls. These results show that inhibition of CK to < 2% of control activity by IA reduced contractile reserve by approximately 50%. We conclude that CK activity is essential for the expression of the full dynamic range of myocardial performance.

Adenylate Kinase↗

PubMed1995

Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries.

The importance of smooth muscle cell pHi and pHo for the hypercapnic vasodilation of rat cerebral arteries was evaluated in vitro. Vessel segments were mounted in a myograph for isometric tension recording; pHi was measured by loading the smooth muscle cells with the fluorescent dye BCECF, and pHo was measured with a glass electrode. In all studies, Ca(2+)-dependent basal tension (in the absence of any agonist) and tension in the presence of arginine vasopressin were investigated. Control solution was physiological saline bubbled with 5% CO2 and containing 25 mmol/L HCO3- (pH 7.45 to 7.50). Induction of hypercapnic acidosis (10% CO2) or normocapnic acidosis (15 mmol/L HCO3-) caused significant inhibition of smooth muscle tension, and both conditions reduced pHi as well as pHo. N-Nitro-L-arginine significantly inhibited the relaxation to hypercapnic acidosis but had no significant effect on relaxation to normocapnic acidosis. Predominant extracellular acidosis, induced by reducing [HCO3-] from 25 to 9 mmol/L and CO2 from 5% to 2.5%, also caused inhibition of tension in steady state. By contrast, predominant intracellular acidosis, induced by increasing [HCO3-] from 25 to 65 mmol/L and CO2 from 5% to 15%, induced a small increase of basal tension and a small decrease of tension in the presence of arginine vasopressin. The responses to predominant intracellular or extracellular acidosis were qualitatively similar in the presence and absence of endothelium and in the presence and absence of N-nitro-L-arginine. It is concluded that the extracellular acidosis and not smooth muscle intracellular acidosis is responsible for the relaxation to hypercapnic acidosis.

Acidosis↗

PubMed1995

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress.

Adenosine Diphosphate↗

PubMed1995

Five new triterpene glycosides from Wisteria brachybotrys (Leguminosae).

From the vines of Wisteria brachybotrys (Leguminosae), five new oleanene glycosides, called wistariasaponins YC1,2, B3 and A2,3, together with four known ones were isolated. Their structures have been elucidated to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-(1-->2)-beta-D- glucuronopyranosyl yunganogenin C 21-O-beta-D-glucopyranoside (1), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->2)-beta -D- glucuronopyranosyl yunganogenin C 21-O-beta-D-glucopyranoside (2), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-(1-->2)-beta- -D-glucuronopyranosyl wistariasapogenol B 30-O-beta-D-glucopyranoside (3), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-(1-->2)-beta-D- glucuronopyranosyl wistartiasapogenol A 30-O-beta-D-glucopyranoside (4) and 3-O-beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl wistariasapogenol A 30-O-beta-D-glucopyranoside (5), respectively.

Carbohydrate Sequence↗

PubMed1995

Changes of plasma endothelin and atrial natriuretic peptide during the onset and after termination of paroxysmal supraventricular tachycardia.

Radioimmunoassays were used to measure the concentration changes of plasma endothelin (ET) and atrial natriuretic peptide (ANP) during the onset and after termination of paroxysmal supraventricular tachycardia (SVT). 30 cases were reviewed and comparisons with 42 normal subjects were made. There are very significant differences (P < 0.0001) in the concentration changes of both plasma ET and ANP during the onset and 30 minutes after the termination of SVT. During the onset period of SVT, the plasma ET and ANP were markedly elevated and 30 minutes after its termination they were lowered significantly, but their concentrations were still 2-fold higher than those of the control group. As the biological effects of ANP and ET are antagonistic to each other, their parallel elevation and lowering of plasma concentrations during and after the termination of SVT reveal that these 2 hormones participate in the pathophysiological process of SVT. This phenomenon is possibly one of the homeostatic regulatory functions in the organism.

Adult↗

PubMed1994

Beta-blockers in cardiac failure.

The use of beta-blocking agents in patients with heart failure is still controversial. An activated sympatho-adrenal system in heart failure may support blood pressure and cardiac index, on the other hand, it increases cardiac load and myocardial oxygen consumption, reduces myocardial oxygen supply and may contribute to the high incidence of arrhythmias and sudden death. Today there is a certain awareness about the important role of the sympatho-adrenal system in CHF. Short-term studies failed to demonstrate a benefit of beta-blockers while long-term studies have proved major haemodynamic benefit and functional improvement in most patients. The haemodynamic benefit consists of a reduction of heart rate and left ventricular filling pressure and an improvement in exercise capacity. The mechanism of these actions of beta-blockers, with the exception of lowering heart rate, remains unclear. Energy metabolism of the failing heart, which is considered to be deficient, may beneficially be influenced by chronic beta-blocker treatment. Effects of beta-blockers on prognosis in patients with heart failure are also still controversial. Most recent trials (MDC Trial, CIBIS Trial) were inconclusive concerning mortality. Aetiology of heart failure may be important; however, observations on secondary prevention post-myocardial infarction also contradict heart failure studies. Thus, further efforts are urgently needed to define the mechanism of action of beta-blockers in patients with cardiac failure and to identify more clearly patients who benefit from this type of therapy.

Adrenergic beta-Antagonists↗

PubMed1994

Effects of LTD4 and its specific antagonist L-660,711 in isolated rat hearts with chronic myocardial infarction.

We investigated the effects of leukotriene (LT) D4 and its novel potent and selective antagonist L-660,711 on isolated rat hearts with chronic myocardial infarction. The left coronary artery was ligated permanently or for 30 or 60 min and followed by reperfusion. Hearts were isolated and perfused in the Langendorff mode 4 days, 4 wk, or 8 wk after the operation. Dose-response curves for LTD4 (12-240 ng/min) on coronary flow were shifted to the left in rats with permanent coronary occlusion for 8 wk or with coronary occlusion for 30 or 60 min and reperfusion for 4 wk. In contrast, dose-response curves were unchanged in rats 4 days after myocardial infarction. L-660,711 shifted dose-response curves for LTD4 on coronary flow to the right in all groups. The negative inotropic and chronotropic effects of LTD4 could be markedly attenuated by L-660,711 in all groups. Our findings suggest that the effect of LTD4 is enhanced in rat hearts with chronic myocardial infarction. L-660,711 effectively antagonized the vasoconstrictor effect of exogenous LTD4.

Angiotensin I↗

PubMed1993

Contractile function of right ventricular papillary muscle after left ventricular infarction in rats: effects of early and late inhibition of angiotensin converting enzyme.

Alterations in the right ventricular function may or may not contribute to progressive cardiac dysfunction after left ventricular infarction. Ligation of the left coronary artery (LCAL) was lethal within 24 h for 25% of 100 rats, whereas none of 21 sham-operated rats died. No rats died during the following 4 weeks, after which the ischaemic area of the left ventricular wall appeared fibrotic and weighed 0.041% of the body weight. Simultaneously, the weight of the right ventricle increased from 0.037 to 0.072% of the body weight. The hypertrophied right papillary muscle had a depressed force of contraction and prolonged contraction and relaxation phases. Angiotensin converting enzyme inhibition (ACEI) started early (24 h) prevented hypertrophy and normalized the contractile pattern under basic conditions. However, isoprenaline stimulation revealed that the relaxation phase was still prolonged. Concentration-effect curves for Ca2+ indicated that the pathological relaxation observed in the hypertrophied muscles and during isoprenaline stimulation of myocardium in ACEI treated animals could be due to insufficient re-uptake of cytosolic Ca2+ by the sarcoplasmic reticulum. The results support the idea that the development of right ventricular hypertrophy may contribute to pathophysiological consequences of an infarct in the left ventricle. ACEI started after 24 h prevented hypertrophy, whereas ACEI started after 14 days did not. ACEI was unable to normalize completely the balance between energy demand and energy delivery.

Angiotensin II↗