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Biomedical subjects

K Hu

Publications and source records attributed to K Hu.

At least 127 records · Page 7Linked to original sources
PubMed1996

Changes of atrial natriuretic peptide in brain areas of rats with chronic myocardial infarction.

We measured immunoreactive atrial natriuretic peptide (ANP) in 18 selected, microdissected brain areas. Rats were studied 8 wk after coronary ligation or sham operation or as nonoperated control animals. In separate animals, hemodynamic and plasma parameters were measured. Rats with myocardial infarction had marked elevated right atrial and left ventricular end-diastolic pressure (2.6 +/- 0.6 and 16.2 +/- 3.1 mmHg, respectively; n = 15) vs. sham-operated rats (1.3 +/- 1.0 and 5.5 +/- 1.2 mmHg, n = 14; P < 0.05) and depressed maximal rate of pressure development (9,613 +/- 980 vs. 15,600 +/- 2,027 mmHg/s; P < 0.05) but similar arterial pressure (126 +/- 4 vs. 124 +/- 3 mmHg; P > 0.05). After myocardial infarction (n = 10), plasma ANP, renin activity, and angiotensin (ANG) II were elevated (53.1 +/- 16.2 pg/ml, 10.7 +/- 2.5 ng ANG I ml-1 h-1, and 219.6 +/- 11.0 fmol/ml, respectively) vs. sham rats (12.0 +/- 2.2 pg/ml, 5.7 +/- 0.7 ng ANG I ml-1, h-1, and 142.9 +/- 9.4 fmol/ml; n = 10; P < 0.05), whereas vasopressin and aldosterone levels remained unchanged among groups. In rats with myocardial infarction, a substantial decrease of ANP was found in the medial preoptic nucleus, the supraoptic nucleus, the subfornical organ, the paraventricular nucleus, and the locus ceruleus. These nuclei are involved in electrolyte, and fluid homeostasis, blood pressure regulation, and modulation of neuroendocrine systems. The mechanism of this reduction and the consequences for systemic adaption or decompensation remain unclear. However, the data suggest that myocardial infarction and chronic left ventricular dysfunction may induce changes of a neurotransmitter in brain.

Animals↗
PubMed1996

Protein kinase C activates ATP-sensitive K+ current in human and rabbit ventricular myocytes.

Mediators involved in ischemia preconditioning such as adenosine and norepinephrine, can activate protein kinase C (PKC), and a variety of observations suggest that both PKC and ATP-sensitive K+ current (I (KATP) play essential roles in ischemic preconditioning. PKC is therefore a candidate to link receptor binding to I(KATP) activation, but it has not been shown whether and how PKC can activate I(KATP) in the heart. The present study was designed to determine whether PKC can activate I(KATP) in rabbit and human ventricular myocytes. Under conditions designed to minimize Na+ and Ca2+ currents, dialysis of rabbit ventricular myocytes with pipette solutions containing reduced [ATP] elicited I(KATP)++, with a 50% effective concentration (EC50)of 260 micromol/L. In cells that failed to show I (KATP) under control conditions, superfusion with 1 micromol/L phorbol 12,13-didecanoate (PDD) elicited I(KATP) in a fashion that depended on pipette [ATP], with an [ATP] EC 50 of 601 micromol/L. PDD-induced I(KATP) activation was concentration dependent, with an EC 50 of 7.1 nmol/L. The highly selective PKC inhibitor bisindolylmaleimide totally prevented I(KATP) activation by PDD, and in blinded experiments, 1 micromol/L PDD elicited I(KATP) in eight of nine cells, whereas its non-PKC-stimulating analogue 4 alpha-PDD failed to elicit I(KATP) in any of the five cells tested (P = .003). Similar experiments were conducted in human ventricular myocytes and showed that 0.1 micromol/L PDD elicited I( KATP) at pipette [ATP] of 100 and 400 micromol/L (five of five cells at each concentration) but not at 1 mmol/L [ATP] (none of five cells). We conclude that PKC activates I(KATP) in rabbit and human ventricular myocytes by reducing channel sensitivity to intracellular ATP. This finding has potentially important implications for understanding the mechanisms of ischemic preconditioning.

Adenosine Triphosphate↗
PubMed1996

[Effect of the cardiac renin-angiotensin system on hypertrophy].

The existence of a cardiac renin-angiotensin-system is confirmed. An influence of AII on growth and mitosis of various cells contributing to cardiac hypertrophy has been shown. Prove for a clinical role would be prevention of hypertrophy and of its complications in patients by specific AII-receptor antagonists in a state of a not-activated systemic renin-angiotensin-system and in absence of mechanical effects. This prove is difficult to obtain.

Angiotensin Receptor Antagonists↗
PubMed1995

Mechanisms of ischemic preconditioning in rat hearts. Involvement of alpha 1B-adrenoceptors, pertussis toxin-sensitive G proteins, and protein kinase C.

BACKGROUND: Ischemic preconditioning attenuates the effects of subsequent sustained ischemia by a mechanism involving adenosine and G proteins in several species. Adenosine is not involved in ischemic preconditioning of rat hearts, the mechanisms of which are poorly understood. METHODS AND RESULTS: Reduction of isometric tension development was used as an index of the effects of ischemia in isolated, Langendorff-perfused rat hearts. Two 5-minute periods of ischemia followed by 10 minutes of reperfusion attenuated the reduction of developed tension caused by 30 minutes of ischemia and 15 minutes of reperfusion. Pretreatment with pertussis toxin (PTX), depletion of norepinephrine stores with reserpine, or blockade of alpha 1-adrenoceptors with prazosin prevented the effects of ischemic preconditioning. Whereas alpha 1B-receptor blockade with chloroethylclonidine blocked ischemic preconditioning, alpha 1A-receptor blockade with 5-methylurapadil had no effect. The alpha-adrenergic agonist phenylephrine mimicked the effects of ischemic preconditioning in a concentration-dependent manner, and pretreatment with PTX prevented the action of maximally effective concentrations of phenylephrine. The protein kinase C activator phorbol 12-myristate 13-acetate mimicked and the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and bisindolylmaleimide prevented ischemic preconditioning. CONCLUSIONS: Ischemic preconditioning in isolated, perfused rat hearts is caused by stimulation of alpha 1B-adrenoceptors by endogenous catecholamines through the activation of protein kinase C via a PTX-sensitive G protein. The PTX-sensitive inhibitory protein Gi, which can be activated by adenosine, muscarinic agonists, and alpha 1-adrenoceptor agonists, may play a central role in ischemic preconditioning mediated by protein kinase C across a broad range of species.

Animals↗
PubMed1995

Investigation of coronary vessels in microscopic dimensions by two- and three-dimensional NMR microscopic imaging in the isolated rat heart. Visualization of vasoactive effects of endothelin 1.

BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. CONCLUSIONS: Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.

Animals↗
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

Detection of human papillomavirus types 16, 18 DNA related sequences in bronchogenic carcinoma by polymerase chain reaction.

In studying the relationship between human papillomavirus (HPV) and bronchogenic carcinoma, "high-risk" HPV 16, 18 DNA sequences were detected in samples from 50 lung cancer patients, 18 patients with benign pulmonary diseases and 4 fetal lung tissues by polymerase chain reaction (PCR) and dot-blot hybridization with biotin-labelled probes. The results showed that HPV 16, 18 DNA related sequences were found in 32% of lung cancer specimens, with 10 cases of HPV 16, 5 cases of HPV 18 and 1 case of both types. 48.15% (13/27) of squamous cell carcinomas were shown to be positive for HPV 16, 18 DNA. In addition, two adenocarcinomas and one small cell carcinoma were positive for HPV 16 DNA. No specimens from benign diseases tissues and fetal lung tissues showed positive results. These results suggest that primary bronchogenic carcinoma is related to HPV infection.

Adenocarcinoma↗
PubMed1995

[A preliminary observation of EcochG and cochlear morphology after cervical sympathectomy in guinea pigs].

In order to examine the effect of sympathetic nerve on the inner ear, we observed the changes of EcochG and ultrastructure of the hair cells before and after cervical sympathectomy in 13 guinea pigs. We also compared the results with those of the contralateral side (as a normal control group). We found that there were morphologic changes in the stereocilia of the hair cells in the surgical side. No changes were found in the thresholds, amplitudes and latencies of EcochG. It seems that the effect of the morphologic changes are too small to be detected in the electrophysiologic experiments.

Animals↗
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↗
PubMed1994

Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction.

BACKGROUND: Remodeling of infarcted and noninfarcted ventricular regions, infarct expansion, shape distortion, and global left ventricular (LV) dilation influence LV performance and survival. The effect of chronic exercise, initiated early or later after infarction, on remodeling, hemodynamics, and survival has not been studied. METHODS AND RESULTS: A total of 156 rats were randomized after coronary artery occlusion or sham operation to remain sedentary or to start with swim training 4 days or 21 days after coronary occlusion, which was continued over 8 weeks (6 days per week, 90 minutes per day). These intervals after coronary artery ligation were chosen because final size of infarction is well reached after 4 days; histological evolution of scar healing is still in progress, and after 21 days, histological scar healing is completed. At 8 weeks, hemodynamics were measured and LV dilation quantitated by passive pressure-volume curves. In groups with small (< or = 35%) and large (> 35%) infarcts, the area enclosed by endocardial circumference, infarct size, LV diameter, scar thickness, and septal thickness were measured in stained transverse serial LV sections to assess aneurysmal shape distortion and the response of infarcted and noninfarcted myocardia. Survival was not influenced by infarction or exercise alone. In rats with small infarcts, LV volume and shape and long-term survival were not altered by chronic exercise initiated early or late after coronary artery ligation. Mortality rose in animals with large infarction as a result of exercise (P < .0001) and was 47.6% with early exercise and 26.7% with late exercise (P < .05, early versus late). Infarct size in rats with early exercise (48 +/- 3%) was similar compared with infarct size of rats with late exercise (46 +/- 2%, P = NS compared with early exercise). Exercise did not affect LV dysfunction (assessed by systolic and end-diastolic pressures and dP/dtmax) in survivors of small and large infarctions. LV volumes increased (P < .05) in sedentary rats by large infarction (n = 13, 0.48 +/- 0.04 mL) compared with volumes after sham operation (n = 33, 0.33 +/- 0.03 mL) and with exercise (early, n = 11, 0.56 +/- 0.04 mL; late, n = 11, 0.65 +/- 0.04; P < .05 versus sedentary). In nonsurvivors from early exercise, the area enclosed by LV endocardial circumference (which corresponds to LV volume) was increased by 195%, LV diameter was increased by 60%, and scar thickness was reduced by 37% (P < .05 versus respective control). Septal thickness increased in survivors by exercise (+25%) but decreased (-28.6%) in nonsurvivors (P < .0001 versus respective control). CONCLUSIONS: Endurance training in rats after small infarction, whether started early or late after left coronary artery ligation, was well tolerated without changes in LV volume, shape, hemodynamics, and long-term survival. Endurance training in rats with large infarction decreased overall survival (P < .0001). In survivors from late exercise, training caused aggravation of global LV dilation without additional shape changes. Endurance training after large infarction caused aggravation of remodeling to a degree that was not compatible with life in 27% of the rats with late exercise and in 48% with early exercise after coronary artery ligation, despite similar exercise. This was explained by extensive remodeling that was most pronounced in nonsurvivors from early exercise. In these rats, severe global LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were observed.

Animals↗
PubMed1994

[An experimental study of the auditory brainstem implant in guinea pigs].

In order to examine the characteristics of the auditory brainstem implant, an animal model with electrical stimulation of the cochlear nucleus in guinea pigs was created. Middle latency response (MLR) to pulsatile electrical stimulation of the cochlear nucleus was recorded from the auditory cortex with bipolar plantinumiridium electrodes and stereotaxic technique. The electrically and acoustically generated MLRs have a similar morphology though there are little differences in the latencies, wave intervals and dynamic ranges. The results indicated that the central auditory pathways can be activated by means of electrical stimulation. The safety of the brain tissue to the electrical stimulation are also discussed.

Acoustic Stimulation↗
PubMed1994

[Indications for ACE inhibitors in the postinfarct period].

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Ventricular remodeling after myocardial infarction. Experimental and clinical studies.

Changes of ischemic myocardium following coronary occlusion, including active and passive functions, and adaptive changes of non-ischemic surviving myocardium have been summarized under the term "left ventricular remodeling" post myocardial infarction. An increase in left ventricular volume may be a consequence, and associated with an adverse prognosis. Although left ventricular dilatation may increase stroke volume and, thus, be compensatory at first, in about one-fifth of patients it ultimately results in progressive dysfunction and heart failure. Major determinants of this process are time, infarct size, infarct location, global left ventricular function assessed 4 days after infarction by radionuclide ejection fraction and right heart catheter (stroke volume), and morphology of the infarct-associated coronary artery. The surviving myocardium hypertrophies and may also dilate structurally. Depression of left ventricular ejection fraction chronically after the infarct is due to deterioration of wall motion of chamber segments initially classified normal by radionuclide analysis. Biochemical changes may also occur, including reduction of phosphocreatine, prolongation of time to peak Cai2+, and changes in myosin isoforms. Systemic or local humoral factors may be involved in these changes, however, clear evidence is still lacking. Perfusion of surviving myocardium may be altered under various conditions due to morphologic and functional changes of coronary vasculature. Successful prevention of heart failure and death by angiotensin converting enzyme inhibitors in asymptomatic patients with left ventricular dysfunction post-myocardial infarction has supported the pathophysiologic concepts of remodeling.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Cardiac dysfunction and development of heart failure.

A major consequence of chronic cardiac dysfunction is chronic overload of contractile myocardium. Various aetiologies, in reaction to this, may induce compensatory mechanisms consisting of excentric (dilatation) and concentric hypertrophy. Chronic left ventricular dysfunction is caused most frequently by myocardial infarction. Left ventricular dilatation and hypertrophy occurs in patients with extensive infarction. Dilatation may at first be compensatory, restoring stroke volume within 4 weeks of the infarct. However, as dilatation progresses, left ventricular ejection fraction and stroke volume deteriorate during exercise and at rest, and finally pulmonary capillary wedge pressure increases and patients become symptomatic 1.5-3 years after the infarct. Major determinants of progressive left ventricular dilatation and deterioration of haemodynamics are a depressed left ventricular ejection fraction, angiographically determined infarct size, stroke volume early (4 days) after myocardial infarction, infarct location (anterior/inferior) and the grade (TIMI) of perfusion of the infarct-associated coronary artery. Chronic loading and unloading may accelerate or decelerate this process. Efficiency and energy reserve (phosphocreatine) of the dilated ventricles is reduced. Further intrinsic changes in surviving myocardium include morphological and functional disturbance of coronary microcirculation.

Cardiomegaly↗
PubMed1993

Effect of acupuncture on weight loss evaluated by adrenal function.

In order to understand the relationship between patients' adrenal function and simple obesity and effect of acupuncture on it, the obesity indices, lipid indices, fasting blood-glucose, noradrenaline, dopamine, adrenalin and cortisol were observed. The results indicated that patients with simple obesity had hypofunction of the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system. Acupuncture treatment not only affected weight loss but also enhanced functioning of the two systems, suggesting that the effect of acupuncture on weight loss may be produced by enhancing the functions of both the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system.

Acupuncture Therapy↗
PubMed1992

Transcription of the hypersensitive site HS2 enhancer in erythroid cells.

In the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site.

Base Sequence↗