Biomedical subjects

H G Zimmer

Publications and source records attributed to H G Zimmer.

At least 37 records · Page 2Linked to original sources

PubMed1996

Functional responses of the left and right heart of diabetic rats to alpha- and beta-adrenergic receptor stimulation.

It was the aim of the present study to examine the influence of alpha-and beta-receptor stimulation on the function of the right (RV) and left (LV) ventricle of streptozotocin-diabetic rats (STZ; 60 mg.kg-1; n = 14). Phenylephrine (PE; 3 mg.kg-1.h-1) or isoproterenol (ISO; 24 micrograms.kg-1.h-1) were infused intravenously for 20 min 4 weeks after STZ injection. The hemodynamic parameters were measured on intact, anaesthetized animals with special Millar ultraminiature tipcatheter manometers. In the non-diabetic animals (n = 15), PE caused a significant elevation of left ventricular systolic pressure (LVSP) from 138.5 +/- 3.2 to 205.4 +/- 7.5 mmHg and raised heart rate (HR) from 362 +/- 12.6 to 399 +/- 17.2 beats.min-1 (mean +/- S.E.M.; P < 0.05). LVSP and HR were significantly lower in the diabetic animals under control conditions (110.5 +/- 6.4 mmHg and 273 +/- 16.0 beats.min-1, respectively) and not affected by PE. ISO induced a significant and comparable decrease in diastolic aortic pressure (DAP) and an increase in HR in both the non-diabetic and diabetic group. The PE-induced enhancements of LV dP/dtmax and RV dP/dtmax from 10533 +/- 805 to 21533 +/- 1386 and from 2044 +/- 262 to 3867 +/- 733 mmHg.s-1 were significant in the control animals. In the diabetic rats, LV dP/dtmax was lower (5971 +/- 901 mmHg.s-1) and was increased by PE to the range of control rats (11171 +/- 1591 mmHg.s-1). The PE-induced elevation of RV dP/dtmax from 2028 +/- 284 to 2771 +/- 391 mmHg.s-1 was less pronounced in the diabetic rats than in the controls. Under the influence of ISO, the increase of dP/dtmax in both ventricles was comparable to the effect of PE and fully preserved in the diabetic animals. Right ventricular systolic pressure (RVSP) was increased under PE and ISO in both groups to comparable values. These results demonstrate that the in vivo response to beta-adrenoceptor stimulation is well preserved in the diabetic rat, while the effects of alpha-stimulation are markedly reduced, especially in the left ventricle and systemic circulation.

Adrenergic alpha-Agonists↗

PubMed1996

Different response of the rat left and right heart to norepinephrine.

The in vivo hemodynamic and morphologic responses of the rat left (LV) and right (RV) ventricle to continuous long-term i.v. infusion of norepinephrine (NE) at different dosages and for different durations of infusion were studied. Female Sprague-Dawley rats received continuous intravenous infusion of norepinephrine from infors syringe pumps for 24, 48 and 72 h at a dose of 200 mu g center dot kg-1 x h-1. Furthermore, NE was infused for 72 h at dosages of 50, 100 and 200 mu g center dot kg-1 x h-1. The beta-adrenergic blocker and vasodilator with alpha1-blocking activity carvedilol (0.5 mg x kg-1 x h-1) was coinfused with NE for 72 h. The hemodynamic effects were measured on intact, anesthetized rats with special Millar ultraminiature pressure tip catheters, and the weights of the left and right ventricles were measured. NE increased heart rate at any time or dose, whereas cardiac output and total peripheral resistance remained unchanged. LV and RV dP/dtmax were nearly doubled as compared to control values and RVSP was elevated by more than 100%. The effect of NE on LVSP was much less pronounced (< 20%) and only significant at 50 mu g x kg-1 x h-1 for 72 h. Neither LV nor RV end-diastolic pressures were elevated, indicating that cardiac failure had not occurred. The LV developed hypertrophy with an increase of the ventricular weight/body weight ratio (LVW/BW) of 22% even after only 2 days of NE (200 mu g x kg-1 center dot h-1). The RV showed no hypertrophy at any time of the experiments. The NE-induced changes in HR, dP/dtmax, RVSP and LVW/BW were completely prevented by the coinfusion of carvedilol. These studies show that the hemodynamic responses to continuous infusion of NE are more pronounced in the RV than in the LV. Conversely, NE induced hypertrophy only in the LV, not in the RV. The hemodynamic effects of chronic NE infusion did not change significantly between 1 and 3 days of infusion. The in vivo responses to exogenous NE therefore were unaffected by adaptive effects such as downregulation of adrenergic receptors.

Animals↗

PubMed1996

Carl Ludwig: the man, his time, his influence.

Carl Ludwig (1816-1895) was the driving force in the foundation and development of scientifically based and experimentally oriented physiology against natural philosophy and vitalism that prevailed during the first quarter of the 19th century in Germany. He was the representative of a small group of young, highly talented and dynamic physiologists aiming at implementing the laws of physics and chemistry as the only active forces in physiologic processes. These "organic physicists" included Emil du Bois-Reymond (1818-1896), Ernst Brücke (1819-1892), and Hermann Helmholz (1821-1894). Carl Ludwig wrote the program of this group in the form of a textbook of physiology that was considered revolutionary, provocative and premature. His academic life, his inventions and discoveries, his scientific achievements, his influence and his personality are reviewed. Since every person can be viewed only in the context of his time, the political background, the economic and social situation, the conditions for science and research as well as the cultural climate that were characteristic for the decisive years of Carl Ludwig are described to some extent. It is shown that Carl Ludwig and his contemporary organic physicists lived and grew into a science- and research-oriented period which had been prepared and paved by men like Johannes Evangelista Purkinje (1787-1869), Ernst Heinrich Weber (1795-1878), Alfred Wilhelm Volkmann (1800-1877), Johannes Müller (1801-1858) and Gustav Theodor Fechner (1801-1887). They benefited from this enormous scientific development and contributed to it to a large and significant extent so that it ultimately turned out to be the most productive and influential period in the history of German physiology. Some of the numerous scholars who had studied with Carl Ludwig carried his approach to physiology into the 20th century: Adolf Fick (1829-1901), Otto Frank (1865-1944), Iwan Petrowitsch Pawlow (1849-1936) and Henry Pickering Browditch (1840-1911).

Germany↗

PubMed1995

Energy metabolism response to calcium activation in isolated rat hearts during development and regression of T3-induced hypertrophy.

The effect of calcium activation on energy production was investigated in isolated perfused hearts from rats treated with triiodothyronine (T3) during 15 days (0.2 mg/kg/day) and in hearts of rats allowed to recover after T3-treatment during 15 days. Changes in phosphorylated compound concentrations were followed in the isolated hearts perfused with a glucose-pyruvate medium by 31P-NMR spectroscopy, when the external calcium concentration was increased from 0.5-1, 1.5 and 2 mM. As expected, T3-treatment resulted in the hypertrophy of the heart (50% increase in HW/BW) that was nearly reversible 15 days after discontinuation of the treatment. When compared to controls, creatine, phosphocreatine (PCr) and glycogen contents were lower (58, 24 and 17% decrease respectively) in the hypertrophied hearts and higher (10, 14 and 18% respectively) after regression of hypertrophy. Intracellular pH, ATP, inorganic phosphate concentrations and the phosphorylation potential were not altered under T3-treatment and after regression of hypertrophy, while calculated free ADP concentration was lower in hypertrophied hearts (control: 40 +/- 2 microM, T3-treatment: 21 +/- 1 microM, regression: 37 +/- 1 microM). Increasing the calcium concentration induced a similar increase in left ventricular developed pressure in the three groups of hearts, with inorganic phosphate concentration increasing with cardiac work. The PCr concentration slightly decreased while the ATP concentration did not change. In spite of different initial PCr concentrations, the evolutions of PCr and Pi concentrations for each stepwise increase in external calcium were similar in the three groups. It is concluded that, in spite of the well-known decrease in efficiency induced by the drug, the mechanisms of PCr (ATP) production remain able to respond to an acute moderate increase in energy demand provoked by a physiological stimulus. This adaptation also persists after the treatment when the energy metabolism balance is apparently improved.

Adenosine Diphosphate↗

PubMed1995

Proto-oncogene expression in the isolated working rat heart: combination of pressure and volume overload with norepinephrine.

We have studied the effects of pressure and volume overload as well as of norepinephrine (NE) alone and in combination on the expression of the proto-oncogenes c-fos and c-myc in isolated perfused working rat hearts. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by Northern blots and quantified with densitometry. Total RNA was isolated from hearts after stimulation with NE (3 x 10(-8) M), after increasing left atrial filling pressure (preload) from 8 to 16 cmH2O, and after elevation of afterload from 80 to 100 cmH2O for 15, 30, 60, 90, and 120 min. NE increased the expression of c-fos and c-myc after 30 and 60 min, respectively. This enhancement occurred at about the same time as that induced by elevation of pre- and afterload, but was more pronounced. Combination of NE with pre- and afterload elevation induced the c-fos mRNA signal to appear earlier and to persist for a longer period of time. Similar results were obtained in regard to the c-myc mRNA, however, the signal was more pronounced in intensity. Simultaneous pre- and afterload increase also led to an earlier expression of the proto-oncogenes and to a longer duration of the signals. These results indicate that the combination of two hypertrophy-inducing stimuli, which may cause a higher degree of cardiac hypertrophy in vivo, induce an earlier, more pronounced and longer-lasting expression of the protooncogenes c-fos and c-myc.

Animals↗

PubMed1995

The functional and metabolic responses of the heart to catecholamines are attenuated in diabetic rats.

Many studies have shown that the contractile response of the rat left ventricle is impaired in diabetes mellitus. Few studies have examined the acute in vivo effects of catecholamines on the right ventricle of diabetic rats. The present study investigates the acute in vivo effects of norepinephrine (100 micrograms.kg-1.h-1 continuous intravenous infusion for 15 minutes) on the function of the right and left ventricle of diabetic rats. The effects of isoproterenol (25 mg.kg-1, subcutaneously) on the activity of glucose-6-phosphate dehydrogenase, the first and rate limiting enzyme of the oxidative pentose phosphate pathway, and on adenine nucleotide biosynthesis of the diabetic heart were also examined. Diabetes mellitus was induced by a single intravenous injection of streptozotocin (60 mg.kg-1) 4 weeks before measurements. The hemodynamic measurements were made on intact, anesthetized rats with Millard ultraminiature pressure tip catheters. The basal hemodynamic measurements (left ventricular systolic pressure, diastolic aortic pressure, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax) as well as glucose-6-phosphate dehydrogenase activity and adenine nucleotide biosynthesis were the same in the diabetic animals as in the controls. Heart rate was slower in the diabetics. Norepinephrine, after 15 minutes of intravenous infusion, induced a marked increase in heart rate, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax; whereas left ventricular systolic pressure and diastolic aortic pressure remained unchanged. Isoproterenol caused a pronounced stimulation of both cardiac glucose-6-phosphate dehydrogenase activity (after 24 hours) and adenine nucleotide biosynthesis (after 5 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

PubMed1995

Cardiac hypertrophy induced by alpha- and beta-adrenergic receptor stimulation.

The aim of the study was to examine whether stimulation of alpha- and beta-adrenergic receptors in intact rats induces cardiac hypertrophy and to characterize the metabolic alterations that precede or accompany the process of hypertrophy. Cardiac beta-adrenergic receptors were stimulated with a single subcutaneous injection of 25 mg/kg isoproterenol. This led to an increase in the cardiac cAMP level which was followed by the sequential enhancement of adenine nucleotide biosynthesis and protein synthesis. The increase in adenine nucleotide and protein synthesis induced by isoproterenol was prevented by propranolol (50 mg/kg) within the first 5 hours. Norepinephrine, given as a continuous intravenous infusion of 0.2 mg/kg for 3 days, induced an increase in heart rate, mean aortic pressure and total peripheral resistance. Cardiac output was slightly reduced. The cardiac RNA/DNA ratio and the left ventricular weight/body weight ratio were significantly increased by about 40%. Simultaneous intravenous administration of the alpha-receptor blocker prazosin (0.1 mg/kg/h) and of the beta-receptor blocker metoprolol (1 mg/kg/h) reversed the functional changes and attenuated the increase in the RNA/DNA ratio induced by norepinephrine. The left ventricular weight/body weight ratio was within the range of the control values. Selective stimulation of alpha-adrenergic receptors by continuous intravenous infusion of norfenephrine (2 mg/kg/h) for 3 days increased heart rate and total peripheral resistance, while cardiac output was significantly lower. The RNA/DNA and left ventricular weight/body weight ratios were increased. Prazosin attenuated the increase in the RNA/DNA ratio induced by norfenephrine and prevented the development of cardiac hypertrophy. In the isolated perfused working rat heart, norepinephrine (3 x 10(-8) M) increased the expression of the proto-oncogenes c-fos and c-myc after 30 and 60 minutes, respectively. This increase occurred at about the same time as that induced by volume overload (increase of preload from 8 to 16 cm H2O) and pressure overload (increase of afterload from 80 to 100 cm H2O), but was more pronounced. In intact rats, norepinephrine elicited an increase in the mRNA and activity of glucose-6-phosphate dehydrogenase, the first and regulating enzyme of the oxidative pentose phosphate pathway, in a time-dependent manner. It is suggested that this may be part of a long-term homeostatic mechanism to keep the cardiac adenine nucleotide level in the normal range.

Animals↗

PubMed1994

Changes in nuclear size of cardiac myocytes during the development and progression of hypertrophy in rats.

It is generally believed that nuclear enlargement indicates polyploidy. The purpose of this study was to establish whether nuclear enlargement is also a marker for cellular hypertrophy. Using isolated myocytes, we examined the growth of cardiac myocyte nuclei during cellular hypertrophy in rats with aortocaval fistulas or left ventricular myocardial infarction. A Coulter Channelyzer was used to measure the volume of the myocytes. Isolated myocytes were stained with the DNA-specific fluorochrome 4'-6-di-amidino-2 phenylindole-HCl for measurements of nuclear length and width, and calculation of nuclear volume. One week, 1 month and 5 months after aortocaval fistula surgery, the nuclear volume of right ventricular myocytes increased by 24, 55 and 56% respectively. Increased length, rather than width, accounted for most of the nuclear growth. Nuclear hypertrophy was associated with a progressive increase in cell volume at each time point (34, 88 and 118%). Adaptive growth of left ventricular myocytes followed the same trend, though the extent of cellular and nuclear hypertrophy was reduced. One month after producing a myocardial infarction, there was an increase in nuclear volume (18%) and nuclear length (11%) in right ventricular myocytes, but no changes in the surviving left ventricular myocytes. The cell volume increased in both right and left ventricles (72 and 18%, respectively). Thus, nuclear size increased as myocytes enlarged, though at a slower rate. Since nuclear DNA content does not increase in rats with aortocaval fistulas or myocardial infarction, the increase in nuclear volume was associated with cellular enlargement rather than increased polyploidy.

Animals↗

PubMed1994

Effects of magnesium orotate on rat heart function.

Female Sprague-Dawley rats were given magnesium orotate (100 mg/kg/day) by gavage for 7 days. The effects on left ventricular, right ventricular, and circulatory function were measured using Millar ultraminiature catheter pressure transducers and thermodilution. In another series, rats were pretreated for 4 days with magnesium orotate. Then they received an intravenous infusion of norepinephrine (0.2 mg/kg/h) for 3 days while magnesium orotate treatment was continued. Thereafter, left ventricular function was examined. Magnesium orotate given for 7 days in control rats induced an increase in heart rate from 380 +/- 18 (n = 7) to 415 +/- 9 beats/min (n = 8); in left ventricular systolic pressure from 165 +/- 8 to 183 +/- 10 mmHg; in left ventricular dP/dtmax from 11486 +/- 1082 to 13300 +/- 909 mmHg/s; and in cardiac output from 386 +/- 38 to 429 +/- 16 ml/kg/min. The pressure-rate product was significantly elevated by magnesium orotate from 54956 +/- 4260 to 66094 +/- 3703 mmHg/min (p < 0.05). Right ventricular systolic pressure was also significantly increased from 34 +/- 1 to 41 +/- 3 mmHg (p < 0.05), and right ventricular dP/dtmax was increased from 2233 +/- 167 to 2857 +/- 489 mmHg/s. Infusion of norepinephrine for 3 days induced an increase in heart rate by 34%, in left ventricular systolic pressure by 10%, in left ventricular dP/dtmax by 88%, in right ventricular systolic pressure by 147%, and in right ventricular dP/dtmax by 100%. Magnesium orotate treatment did not significantly affect the changes induced by norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Function and energy metabolism of isolated hearts obtained from hyperthyroid spontaneously hypertensive rats (SHR). A 31P-nuclear magnetic resonance study.

It was the aim of this study to evaluate the effects of hyperthyroidism on heart function and cardiac energy metabolism of spontaneously hypertensive (SHR) rats. Hyperthyroidism was induced by daily injections of T3 (0.2 mg/kg s.c.) for 14 days. The hearts were then isolated and perfused in the Langendorff mode. ATP, phosphocreatine (PCr), and inorganic phosphate (Pi) were measured continuously by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Work load was altered by varying stepwise the Ca++ concentration in the perfusion fluid from 0.5 to 1.0, 1.5, and 2.0 mM, respectively. At every elevation of the Ca++ concentration, the increase in left ventricular developed pressure (LVDP) was higher in the hyperthyroid SHR than in the untreated SHR hearts. The ATP and PCr concentrations were lower in the hyperthyroid SHR compared to the untreated SHR hearts throughout the perfusion period. PCr decreased at every Ca++ elevation in both the untreated and hyperthyroid SHR hearts. The PCr/ATP ratio was not altered at any Ca++ concentration neither in the untreated SHR nor in the hyperthyroid SHR hearts. The Ca(++)-induced stepwise elevation in LVDP was higher at any given PCr/Pi ratio in the hyperthyroid SHR than in the untreated SHR hearts. Thus, the Ca(++)-inducible contractile reserve was greater in the hyperthyroid SHR heart.

Adenosine Triphosphate↗

PubMed1993

Effect of pressure and volume overload on proto-oncogene expression in the isolated working rat heart.

OBJECTIVE: The aim was to study the effect of pressure and volume overload on the expression of the proto-oncogenes, c-fos and c-myc, in isolated perfused working rat hearts and to compare these results with the known effects of noradrenaline. METHODS: Working rat hearts were obtained by converting the Langendorff preparation into the working mode by perfusion through the left atrium. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by northern blots and quantified with densitometry. Total RNA was isolated from hearts after stimulation with noradrenaline (3 x 10(-8) M), after increasing afterload from 80 to 100 cm H2O, and left atrial filling pressure (preload) from 8 to 16 cm H2O for 15, 30, 60, 90, and 120 min, respectively. RESULTS: The mRNAs of c-fos and c-myc were not detectable in freshly excised rat hearts. When the hearts were perfused in the working mode for 15, 30, 60, 90, and 120 min, c-fos and c-myc mRNAs were measurable, and these mRNA levels served as control baseline values that were set at 100%. When noradrenaline was infused, c-fos mRNA was increased fivefold after 30, threefold after 60, and 3.8-fold after 90 min. The mRNA of c-myc was increased 1.8-fold after 60 min and 3.8-fold after 90 min. The increase in afterload induced a threefold increase of c-fos mRNA after 30 min and a threefold increase of c-myc mRNA after 90 min. When preload was increased, c-fos mRNA rose 1.8-fold after 30 min, and c-myc mRNA twofold after 60 min and 2.8-fold after 90 min compared to the controls. CONCLUSIONS: Pressure and volume overload have effects on the expression of c-fos and c-myc mRNA that are similar to those obtained with noradrenaline stimulation which induced the most pronounced signals. Our time course studies showed that c-fos mRNA always rose before c-myc mRNA. This common sequential induction pattern may have important signal function in the processes that trigger the development of cardiac hypertrophy.

Animals↗

PubMed1993

Acute effects of catecholamines on function of the rat right heart.

OBJECTIVE: Although the haemodynamic effects of catecholamines on the rat left ventricle have been investigated extensively, only few systematic in vivo studies have been performed on the right ventricle. The aim was to examine the acute effects of noradrenaline and isoproterenol on rat right ventricular function. METHODS: Haemodynamic variables were measured during acute, 20 minute infusion of noradrenaline (0.1 mg.kg-1 x h-1) or isoproterenol (12 micrograms.kg-1 x h-1) in female Sprague Dawley rats. To estimate the contribution of alpha and beta receptor stimulation to these effects, eight rats each were infused with prazosin (0.1 mg.kg-1 x h-1), metoprolol (1.0 mg.kg-1 x h-1), or the alpha and beta antagonist carvedilol (0.5 and 1.0 mg.kg-1 x h-1) alone and in combination with noradrenaline or isoproterenol. RESULTS: Noradrenaline and isoproterenol increased right ventricular systolic pressure (RVSP) from 30.3 (SEM 0.5) (n = 32) to 72.7(2.7) (n = 24) and 72.3(4.4) (n = 8) mm Hg, right ventricular (RV) dP/dtmax from 1848(70.3) to 4058(301) and 3612(366) mm Hg.s-1, and heart rate from 329(6) to 371(6) and 420(8) beats.min-1, respectively. Metoprolol completely prevented the isoproterenol induced haemodynamic changes, but neither metoprolol nor prazosin was able to significantly affect the pressure effect of noradrenaline (noradrenaline + metoprolol: 67.3(6.9) mm Hg, noradrenaline + prazosin: 67.0(3.8) mm Hg). The combination of both blockers, however, prevented the noradrenaline induced rise in RVSP (noradrenaline + metoprolol + prazosin: 36.5(5.1), and noradrenaline + prazosin + metoprolol: 30.0(1.2) mm Hg). Carvedilol (1.0 mg.kg-1 x h-1) significantly attenuated the noradrenaline induced RVSP increase (39.1(3.0) mm Hg), but not to the control range. Metoprolol or carvedilol completely prevented the noradrenaline elicited increases in heart rate (254(7) and 287(20) min-1) and RVdP/dtmax, but prazosin alone had no effect on the heart rate and RVdP/dtmax increase. Thus beta receptor blockade alone failed to significantly influence the noradrenaline induced increase of RVSP despite prevention of the increase in heart rate and RVdP/dtmax. Prazosin had a significant effect on RVSP only in combination with metoprolol. CONCLUSIONS: The combined effect of both alpha and beta blockade exceeds the pure addition of the single effects in the rat right ventricle. Moreover, we speculate that the failure to reduce the noradrenaline induced increase in RVSP by either alpha or beta blockade alone is due to the stimulation of the receptor that is not affected by the respective blocker.

Adrenergic beta-Antagonists↗

PubMed1993

Norepinephrine-induced changes in rat heart function, metabolism, and weight are antagonized by carvedilol.

One aim of our study was to characterize in intact rats the pharmacologic effects of carvedilol. After 3 days of continuous intravenous (i.v.) infusion of carvedilol (0.5 mg/kg/h), the positive chronotropic and inotropic effects of i.v. bolus injections of isoproterenol (0.1, 0.3, and 1 microgram/kg) and phenylephrine (3, 10, and 30 micrograms/kg), respectively, were measured and compared with those obtained in rats that received a continuous i.v. infusion of 0.9% NaCl, prazosin (0.1 mg/kg/h), and propranolol (0.5 mg/kg/h). The chronotropic response to isoproterenol was less blunted in carvedilol-treated animals than in propranolol-treated animals. The pressure response to phenylephrine was attenuated only moderately. Thus, carvedilol had beta-receptor blocking actions on intact rat heart that were similar to but not as pronounced as those of propranolol. Because it reduced diastolic aortic pressure (DAP) and left ventricular systolic pressure (LVSP), it also had a moderate vasodilating effect. Carvedilol (continuous i.v. infusion of 0.25 and 0.5 mg/kg/h) antagonized the effects of norepinephrine (NE, i.v. infusion of 0.2 mg/kg/h for 3 days) on heart function and heart weight in a dose-dependent manner. It also attenuated markedly the norepinephrine (NE)-induced increase in the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (PPP), although a 37% stimulation persisted.

Adrenergic beta-Antagonists↗

PubMed1993

Alteration of cardiac energy state during development of hypertension in rats of the Lyon strain: a 31P-NMR study on the isolated rat heart.

The effect of different chronic blood pressure levels on cardiac energy metabolism was studied by 31P-NMR spectroscopy in perfused hearts from the Lyon strains of hypertensive (LH), normotensive (LN) and hypotensive (LL) rats at the ages of 12 and 21 weeks. The in vivo assessment of haemodynamic parameters measured at 21 weeks in anaesthetized rats with an ultraminiature catheter pressure transducer confirmed that left ventricular systolic pressure and mean aortic pressure were significantly greater (+25%) in LH rats than in LN and LL rats. In the LL animals, left ventricular systolic pressure was slightly reduced (-10%) and cardiac contractility (estimated by LV dP/dtmax) showed a 24% decreased compared to normotensive animals. The energy state of the cardiomyocytes was characterized at different work levels of isolated rat hearts, by determining the concentration of the free phosphorylated compounds at each work level. Changes in workload were induced by varying the calcium concentration in the perfusion fluid. Increasing extracellular calcium concentration resulted in a similar increase in left ventricular developed pressure (LVDP) in all groups studied. Intracellular pH was not influenced by either the age of the animals or the level of cardiac work, in the three groups of animals. ATP content of the LN and LL rats remained constant during the whole perfusion period while the 12 week-old LH rats showed a decreased ATP content with increasing cardiac work. In the older LH rats, ATP content was decreased at the highest work level (corresponding to 2 mM calcium). In response to the increase in work, phosphocreatine (PCr) content diminished and inorganic phosphate (Pi) content increased in both LN, LH and LL animals. PCr degradation and Pi accumulation were higher in the LH rats and less in LL rats compared to the LN. These changes were more important in the younger than in the older hypertensive animals. The relationship between LVDP and [Pi]/[PCr] indicates that oxidative metabolism is maximally activated in the young hypertensive rats and suggests that this maximal activation represents an adaptive phase to the increase in blood pressure. Since the difference between the metabolic pattern of the 21 week-old LH rats and age-matched LN rats was less pronounced, it is likely that a compensatory stage has been reached at that age.

Animals↗

PubMed1993

Cardiovascular response to triiodothyronine in Sprague-Dawley and spontaneously hypertensive rats.

In this study we have compared the influence of triiodothyronine (T3) on cardiovascular function and heart weight in Sprague-Dawley and spontaneously hypertensive rats. We also investigated whether the effects induced by T3 are reversible. T3 was administered daily (0.2 mg/kg subcutaneously) for 14 days in female Sprague-Dawley and spontaneously hypertensive rats. Treatment was then stopped for 14 days. At the end of the treatment and of the period without T3, hemodynamic measurements were made in the intact, anesthetized animals by catheterization of the left ventricle with a Millar ultraminiature catheter pressure transducer. Cardiac output was measured by thermodilution. The development and regression of myocardial hypertrophy was measured by the ratio of heart to body weight. The systolic pressure in the left ventricle was higher in spontaneously hypertensive rats than in Sprague-Dawley rats matched for body weight. At the end of treatment with T3, the heart rate was increased to exactly the same extent in both groups. Left ventricular systolic pressure was increased by 15% in Sprague-Dawley rats, but was not altered significantly in spontaneously hypertensive rats. T3 induced an increase in left ventricular dp/dtmax by 106% in Sprague-Dawley rats, but by only 32% in spontaneously hypertensive rats. Cardiac output increased by 63% in Sprague-Dawley rats, but by only 31% in spontaneously hypertensive rats (statistically not significant). When T3 treatment was stopped for 14 days, all the functional changes returned to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effects of ribose on exercise-induced ischaemia in stable coronary artery disease.

There is no established treatment specifically aimed at protecting or restoring cardiac energy metabolism, which is greatly impaired by ischaemia. Even after reperfusion, myocardial content of ATP remains low for more than 72 h. Long-term post-ischaemic dysfunction and irreversibility of ischaemic damage have been associated with low ATP content. Evidence that the pentose sugar ribose stimulates ATP synthesis and improves cardiac function led us to test the possibility that ribose increases tolerance to myocardial ischaemia in patients with coronary artery disease (CAD). 20 men with documented severe CAD underwent two symptom-limited treadmill exercise tests on 2 consecutive days; we postulated that the ischaemia induced might bring about changes in ATP metabolism lasting for several days. Patients whose baseline tests showed reproducibility were randomly allocated 3 days of treatment with placebo or ribose 60 g daily in four doses by mouth. Exercise testing was repeated after treatment on day 5. At that time mean (95% confidence interval) treadmill walking time until 1 mm ST-segment depression was significantly greater in the ribose than in the placebo group (276 [220-331] vs 223 [188-259] s; p = 0.002). The groups did not differ significantly in time to moderate angina. In the ribose-treated group the changes from baseline to day 5 in both time to ST depression and time to moderate angina were significant (p less than 0.005), but these changes were not significant in the placebo group. In patients with CAD, administration of ribose by mouth for 3 days improved the heart's tolerance to ischaemia. The presumed effects on cardiac energy metabolism offer new possibilities for adjunctive medical treatment of myocardial ischaemia.

Aged↗

PubMed1992

Nuclear DNA content and nucleation patterns in rat cardiac myocytes from different models of cardiac hypertrophy.

Nuclear DNA content and number of nuclei were examined in cardiac myocytes isolated from controls and rats with volume and pressure overload hypertrophy to determine if haemodynamic overload alters these nuclear parameters. The experimental groups were comprised of normotensive (WKY) and Spontaneously Hypertensive rats (SHR). Additionally, Sprague-Dawley rats with aortic constriction (AC), pulmonary stenosis (PS), myocardial infarction (MI), and 5 month arteriovenous fistulas (F) were studied along with appropriate shams for each of these groups. Nuclear DNA content was measured from DAPI-stained nuclei using an image analysis microdensitometry system. Myocyte volume was measured with a Coulter Channelyzer system. Approximately 83% of the left ventricular myocytes from the SHR and WKY groups contained a diploid DNA content with the remainder being tetraploid. The remaining experimental and sham groups, all female Sprague-Dawley rats (SD), were approximately 93% diploid. The nucleation patterns differed slightly between rat strains with the SHR/WKY expressing approximately 85% binucleation, 14% mononucleation and 5% tri- or tetranucleation. All SD groups, control and hypertrophied, showed approximately 89% binucleation, and 10% mononucleation with the remainder being tri- or tetranucleated. In summary: (1) cardiac myocytes from SHR/WKY strains are predominantly diploid but to a lesser degree than myocytes from SD; (2) nuclear number follows the same pattern with SHR/WKY showing a smaller percentage of binucleated myocytes than SD myocytes; (3) neither the duration, severity, or type of overload caused a significant change in the extent of polyploidy in overloaded hearts from SD rats; and (4) the extent of polyploidy in cardiac myocytes from both the right and left ventricles of SHR and WKY animals does not differ statistically.

Animals↗

PubMed1992

Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

To examine whether stimulation of alpha-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the alpha-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the beta-receptor blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7 +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗