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H H Klein

Publications and source records attributed to H H Klein.

At least 73 records · Page 4Linked to original sources
PubMed1993

Interstitial myocardial neutrophil accumulation between 3 and 72 h of reperfusion does not significantly affect infarct size in porcine hearts.

The inflammatory response--mediated by activated neutrophils--is assumed to play an important role in the pathogenesis of reperfusion injury. This study investigated whether extravascular myocardial neutrophil accumulation between 3 and 72 h of reperfusion affects infarct size in porcine hearts. The left anterior descending coronary artery was ligated distally in 24 pigs for 45 min and reperfused for 3 h (n = 8), 24 h (n = 8), or 72 h (n = 8). Infarct size and extravascular myocardial accumulation of neutrophils was evaluated at the end of the experiments. Global hemodynamic characteristics were comparable for the three groups both before and during ischemia. Neutrophil count/mm2 reperfused myocardium increased substantially from 4 +/- 2 (3 h of reperfusion) to 129 +/- 70 (24 h of reperfusion, p < 0.001). After 3 d of reperfusion, the neutrophil count had decreased to 10 +/- 7. The invasion of neutrophils between 3 and 24 h of reperfusion did not significantly affect the extent of myocardial necrosis. Infarct sizes after 3 h (62.6 +/- 20%), 24 h (71.8 +/- 13%), and 72 h of reperfusion (67.6 +/- 18%) did not differ significantly. This finding does not suggest that a significant amount of myocytes are destroyed by extravasated neutrophils between 3 and 72 h of reperfusion.

Animals↗
PubMed1993

Cytomegalovirus associated inflammatory heart muscle disease.

Cytomegaloviruses(CMV) belong to a group of cardiotropic DNA-viruses with well-documented but sporadic cardiac involvement. By in situ hybridization with a biotinylated cDNA probe CMV-DNA was analysed in 2 different series of patients(1982-1988; 1989-1991) in the endomyocardial biopsy specimens of 35 patients with active myocarditis as defined by the Dallas criteria, and of 35 patients with acute perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality and/or an endomyocardial biopsy positive for active myocarditis) were analysed. 51% of patients with active myocarditis, 65% positive findings were observed in patients with perimyocarditis when all positive signals in the myocardium were taken into account. Since in interstitial cells and the vascular endothelium HCMV-DNA was also detected in controls we conclude that only HCMV-DNA in the nuclei are specific for HCMV-associated myocarditis. The incidence of positive signals in the myocytes was lower: 14% of all myocarditis patients and 8.5% of all pericarditis patients demonstrated this pattern. The results from in situ hybridization were compared to circulating anti-CMV antibodies from by an ELISA. As possible predisposing immunologic factors or associated alterations of effector functions we found a shift from normal to reduced natural killer cell activity and a marginal increase in B- and activated T-cells in the peripheral blood.

Adult↗
PubMed1992

Evidence that metformin increases insulin-stimulated glucose transport by potentiating insulin-induced translocation of glucose transporters from an intracellular pool to the cell surface in rat adipocytes.

To examine the cellular mechanism of the antihyperglycemic action of metformin (M) we studied the effect of M on various functional and molecular parameters involved in the pathogenesis of insulin resistance. Isolated rat adipocytes were incubated with or without M (1-100 micrograms/ml) for 2 hours at 37 degrees C followed by an incubation with or without insulin (I) (10) ng/ml). M-treatment had no significant effect on basal (B) 3-O-methylglucose uptake. In contrast, M increased I-stimulated glucose transport in a dose dependent manner up to 43 +/- 7%. This effect was neither associated with a significant effect of M on trace insulin binding, 1.74 +/- .2% (-M) vs 1.89 +/- .3% (+M), p > 0.05, nor with an effect of M on in vivo activation of insulin receptor kinase activity as measured by 32P-incorporation into the 95 kDa beta-subunit of the insulin receptor and an exogenous substrate, histone 2B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Myocardial distribution of indium-111-antimyosin Fab and technetium-99m-sestamibi in experimental nontransmural infarction.

Early revascularization in acute myocardial infarction results in normal, necrotic and partially damaged and partially salvaged ("intermediate") myocardium. By combining a perfusion tracer and a marker for myocardial injury, we attempted to differentiate between these three types of cardiac tissue. The LAD was occluded in nine pigs for 45 min and then reperfused. After 48 and 72 hr, 74 MBq 111In-antimyosin Fab and 740 MBq 99mTc-sestamibi, respectively, were injected intravenously. Normally perfused myocardium was labeled with fluorescein and the heart excised. Three to four slices were cut from the apex. Tetrazolium staining revealed the zone of necrosis. Tracer distribution on double-nuclide scintigrams of the slices also reflected the three different myocardial zones. Guided by fluorescence and macrohistochemistry, tissue samples were excised from each zone. In relation to normal myocardium, mean activity in the intermediate zone was 0.82 +/- 0.20 for 99mTc-sestamibi and 2.84 +/- 1.31 for 111In-antimyosin Fab. Activity in necrotic myocardium was 0.30 +/- 0.19 and 3.95 +/- 2.47, respectively. These results show that 111In-antimyosin Fab fragments not only accumulate in necrotic but also in intermediate myocardium. Therefore, an overestimation of infarct size may occur if 111In-antimyosin Fab fragments are used alone without a perfusion tracer.

Animals↗
PubMed1991

The relationship between insulin binding, insulin activation of insulin-receptor tyrosine kinase, and insulin stimulation of glucose uptake in isolated rat adipocytes. Effects of isoprenaline.

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.

3-O-Methylglucose↗
PubMed1991

[Significance of electro- and echocardiogram for the diagnosis of cardial amyloidosis].

The cause of severe right heart failure and of equal diastolic pressures in both ventricles (as seen in constrictive pericarditis) in a 56-year-old woman was suspected to be cardiac amyloidosis on the basis of findings in both the echocardiogram (biventricular hypertrophy) and the electrocardiogram (prominent Q waves, absent hypertrophy signs). The endomyocardial biopsy was at first unremarkable. But later, serial modified Congo-red staining unequivocally demonstrated amyloid deposits. In a second case, a 66-year-old man with global cardiac failure and echocardiographic pointers towards hypertrophic cardiomyopathy, was treated with verapamil, 240 mg daily. When this was not tolerated he was hospitalized. He, too, had prominent Q waves but no signs of ventricular hypertrophy. Cardiac amyloidosis was confirmed by biopsy. Both cases underline the special importance of echo- and electrocardiographic changes, taken together, in the diagnosis of cardiac amyloidosis.

Aged↗
PubMed1991

Failure of iloprost to protect the regionally ischemic, reperfused porcine heart.

The effect of iloprost (Schering AG, Berlin), a stable prostacyclin analogue, was investigated in ischemic, reperfused porcine hearts. The left anterior descending coronary artery (LAD) was distally occluded in 18 pigs for 45 min followed by 3-d of reperfusion. Nine pigs were continuously treated with iloprost at a dose of 25 ng/kg per min. Treatment was started as intracoronary infusion into the proximal LAD 10 min before occlusion. The intercoronary infusion was replaced by an intravenous infusion after 45 min of reperfusion, which was continued until the end of the experiment. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Myocardial concentrations of adenosine triphosphate were evaluated at the end of the experiment. Generation of free radicals by stimulated polymorphonuclear neutrophils was determined by luminol-enhanced chemiluminescence. Histologic and immunohistologic techniques were applied to characterize the myocardial inflammatory response. Global hemodynamics did not differ between the two groups. Neither infarct size (control group 68 +/- 18%, treated group 74 +/- 14%), recovery of systolic shortening (control group 3 +/- 6%, treated group 6 +/- 6%), nor myocardial adenosine triphosphate concentrations were improved by iloprost treatment. Myocardial inflammatory response remained unaffected by this treatment. The capacity of coronary venous, stimulated polymorphonuclear neutrophils to generate free radicals was slightly suppressed in the treated group before ischemia, at the end of ischemia and during early reperfusion. In this preparation, iloprost did not exhibit any beneficial effect on infarct size, recovery of systolic shortening and myocardial adenosine triphosphate concentrations.

Adenosine Triphosphate↗
PubMed1991

The effects of Trolox, a water-soluble vitamin E analogue, in regionally ischemic, reperfused porcine hearts.

Myocardial protection by the water-soluble vitamin E analogue, Trolox, was investigated in 18 regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally ligated for 45 min and was reperfused for three days. Five grams of Trolox (n = 9) were infused intravenously before coronary occlusion. Treatment was continued with an intravenous dose of 5 grams Trolox/24 hours until the end of the experiment. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Generation of free radicals by stimulated neutrophils was evaluated by luminol-enhanced chemiluminescence. Plasma concentrations of Trolox were measured by high-performance liquid chromatography. Aside from heart rate before ischemia, global hemodynamic values including calculated left ventricular oxygen consumption did not differ significantly between the two groups. Plasma concentrations of Trolox measured 1.8 +/- 0.3 mmol/l (before ischemia), 0.96 +/- 0.13 mmol/l (before reperfusion), 0.77 +/- 0.1 mmol/l (40 min of reperfusion), and 0.08 mmol/l (end of the experiment). Generation of free radicals by stimulated neutrophils was reduced by about 30% in the treatment group before ischemia and immediately before reperfusion, but was not reduced at the end of the experiment. Risk regions (control group 19.4 +/- 6 g, treatment group 19.3 +/- 7 g) and infarct sizes (control group 69.3 +/- 8%, treatment group 69.3 +/- 12%) were almost identical. Regional systolic shortening of a control segment and of the risk region were similar in both groups before ischemia, before reperfusion, and after 45 min of reperfusion. After 3 days of reperfusion, regional systolic shortening of the reperfused myocardium of the treated group had recovered to a significantly greater extent (P = 0.027). This parameter amounted to 9 +/- 6% in the treated group and to 3 +/- 3% in the control group. Improved functional recovery was not accompanied by higher tissue concentrations of adenosine triphosphate. It is concluded that the chosen treatment with Trolox does not reduce infarct size but accelerates functional recovery. This finding suggests that the mechanisms resulting in myocardial necrosis during ischemia/reperfusion and in post-ischemic myocardial dysfunction may differ.

Adenosine Triphosphate↗
PubMed1991

Modulation of the inflammatory response in experimental myocardial infarction.

The role of inflammation in reperfused, ischaemic myocardium was assessed morphologically in 39 porcine hearts after 24 h (n = 23) and 72 h (n = 16) of reperfusion and after different antiphlogistic treatments. The left anterior descending coronary artery (LAD) was occluded distally for 45 min. Seven pigs received BW755C (10 mg kg-1) i.v. prior to ischaemia (A), eight pigs were given the same dose before 24 h of reperfusion (B), and eight pigs were treated with iloprost (25 ng kg-1 min-1) i.v. before occlusion and continuously for 72 h (C). Two groups of eight pigs each served as controls for 24 h (D) and 72 h (E) of reperfusion. Infarct sizes were determined, myocardium was investigated by light microscopy, and polymorphonuclear leucocytes (PMNs) and macrophages were quantitated after histo- and immunohistochemical staining. Jeopardized myocardium contained 129 neutrophils mm-2 and 120 macrophages mm-2 (D) vs 10 neutrophils mm-2 and 290 macrophages mm-2 (E). Neutrophils and infarct sizes were only significantly decreased in group A (68 neutrophils mm-2, 30% reduction of infarct size). Macrophages infiltration was not significantly affected for all treatment groups (A, B, C). It is concluded that myocardial infarct sizes are neutrophil-mediated postischaemic tissue injury can be reduced by BW755C applied prior to ischaemia. Neutrophil-mediated myocardial injury is unlikely to occur beyond 3 days of reperfusion.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1991

Association of Metformin's effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes.

To examine the cellular mechanism of the antihyperglycemic action of metformin, we studied its effect on various functional and molecular parameters involved in the pathogenesis of insulin resistance. Isolated rat adipocytes were incubated with or without metformin (1-100 micrograms/ml) for 2 h at 37 degrees C followed by an incubation with or without insulin (1.72 nM). Metformin treatment had no significant effect on basal 3-O-methylglucose uptake. In contrast, metformin increased insulin-stimulated glucose transport in a dose-dependent manner up to 43 +/- 7%. This effect was neither associated with a significant effect of metformin on trace insulin binding (1.74 +/- 0.20% without metformin vs. 1.89 +/- 0.30% with metformin; P greater than 0.05) nor with an effect of metformin on insulin-receptor kinase activity as measured by 32P incorporation into the 95,000-Mr beta-subunit of the insulin receptor and an exogenous substrate, histone 2B.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1990

Energy-conserving programming of VVI pacemakers: a telemetry-supported, long-term, follow-up study.

Thirty patients with VVI pacemakers (Quantum 253-09, 253-19, Intermedics Inc., Freeport, TX) were observed for a mean of 65 months. Within 12 months after implantation, optimized output programming was performed in 29 patients. This included a decrease in pulse amplitude (22 patients), pulse width (4 patients), and/or pacing rate (11 patients). After 65 months postimplantation, telemetered battery voltage and battery impedance were compared with the predicted values expected when the pulse generator constantly stimulates at nominal program conditions (heart rate 72.3 beats/min, pulse amplitude 5.4 V, pulse width 0.61 ms). Instead of an expected cell voltage of 2.6 V and a cell impedance of 10 k omega mean telemetered values amounted to 2.78 V and 1.4 k omega, respectively. These data correspond to a battery age of 12-15 months at nominal program conditions. This long-term follow-up study suggests that adequate programming will extend battery longevity and thus pulse generator survival in many patients.

Adult↗
PubMed1990

Delayed improvement of myocardial function after recanalization of a chronic coronary occlusion in a patient with intractable heart failure.

This case report describes the delayed improvement of left ventricular function by recanalization of an occluded coronary artery in a patient with intractable heart failure and three-vessel disease. The left anterior descending coronary artery was occluded distal to the first septal branch, the dominant right coronary artery had a diameter stenosis of 70-80% in its middle part, and the circumflex artery a proximal stenosis of 50%. Ventriculography revealed globally depressed left ventricular function with an ejection fraction of 16%. Successful recanalization and angioplasty of the occluded coronary artery resulted in a slow improvement of left ventricular function. Ultimate recovery of systolic performance (increase of ejection fraction from 16% to 48-51%) required more than half a year. It is speculated that stunned myocardium following chronic ischaemia is a consequence of vascular dysfunction.

Angioplasty, Balloon, Coronary↗
PubMed1990

Stimulation characteristics of a steroid-eluting electrode compared with three conventional electrodes.

Stimulation thresholds of a steroid-eluting electrode (Medtronic CapSure 4003, 9 patients) were compared with three conventional electrodes (carbon-tipped lead, Siemens-Elema 423 S/60, 10 patients; Elgiloy-tipped lead, Cordis Encor, 10 patients; platinum-tipped lead, Telectronix Laserdish 030-276, 9 patients). Voltage thresholds were determined during implantation, 1-3 days, 6 weeks, and 6 months postimplantation. No significant difference among the four electrodes was found in regard to stimulation and sensing behavior during implantation. Compared to intraoperative measurements, mean increase in voltage threshold and absolute voltage thresholds were substantially less for the steroid-eluting electrode than for the other tested electrodes 6 weeks and 6 months after implantation. The rheobasechronaxie product, a parameter of the stimulation performance of electrodes, underlined the superior pacing characteristics of the steroid-eluting electrode. To achieve low chronic stimulation threshold by pharmacological means is an attractive direction for future electrode technology.

Adult↗
PubMed1990

Potential mechanism of insulin resistance in ageing: impaired insulin-stimulated glucose transport due to a depletion of the intracellular pool of glucose transporters in Fischer rat adipocytes.

To examine the cellular mechanism responsible for impaired insulin action in ageing, we determined various in-vitro parameters involved in the pathogenesis of insulin resistance, i.e. basal and insulin-stimulated [14C]3-O-methylglucose transport (3OMG), 125I-labelled insulin binding, activation of insulin receptor kinase (IRKA) in intact cells, and number and subcellular distribution of glucose transporters in subcellular membrane fractions of adipocytes from 6- (FR-6) and 24- (FR-24) month-old Fischer rats. Ageing had no effect on basal 3OMG (12 +/- 4 vs 13 +/- 3 fmol/5 x 10(4) cells, means +/- S.E.M.); in contrast, in FR-24 rats insulin-stimulated 3OMG was markedly decreased by 43% when compared with that in FR-6 rats (158 +/- 14 vs 90 +/- 8 fmol/5 x 10(4) cells; P less than 0.01). Insulin binding to adipocytes from FR-6 rats was 2.40 +/- 0.38% compared with 2.28 +/- 0.47% in FR-24 (P not significant). Moreover, ageing had no significant effect on IRKA, as determined by insulin-stimulated (0, 1, 4 and 500 ng insulin/ml) 32P-incorporation into histone 2B. In subcellular membrane fractions, low density microsomes and plasma membranes, glucose transporter numbers were determined using [3H]cytochalasin B binding and immunodetection using an antiserum against the C-terminal peptide of the hepatoma-G2-glucose transporter. Cytochalasin B binding revealed that in the basal state the intracellular pool of glucose transporters was depleted in FR-24 by about 39% compared with low density microsomes from FR-6: (48.6 +/- 7.2 vs 29.8 +/- 5.5 pmol/mg membrane protein; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1990

Clinical experience with nisoldipine in patients with atrio-ventricular blocks.

The effect of the 1,4-dihydropyridine calcium antagonist nisoldipine (Bay k 5552) on the atrio-ventricular (AV) conduction was studied in 9 patients with AV blocks. The impuls propagation through the AV node (A-H time) and the bundle of His (H-V time) was determined before, 1-3 min and 10-15 min after the intravenous injection of nisoldipine (1.5 micrograms/kg body weight). Except for one patient, A-H and H-V times almost remained unaffected by the calcium antagonist. In this patient with an AV block II, Mobitz type I, A-H time transiently increased from 290 to 410 ms. Nisoldipine did not aggravate an AV block I or II to an AV block II or III, respectively. Furthermore, ventricular heart rates did not change significantly. It is concluded that, in general, nisoldipine does not impair the impulse propagation of the AV node in patients with AV blocks although a transient increase of the A-H time may occur.

Aged↗
PubMed1989

Comparative study on the enhancement of ischemic tolerance by intracoronary pretreatment with three calcium antagonists in pig hearts.

The effect of intracoronary (IC) pretreatment with different calcium antagonists (diltiazem, nifedipine, verapamil) on the development of infarcts was investigated in two experimental series including 35 open-chest pigs. The left anterior descending coronary artery (LAD) was distally ligated for 75 minutes (series A) or for 45 minutes (series B) and was reperfused for 24 hours. Infarct size was determined as the ratio of infarcted myocardium (tetrazolium stain) to the risk region (dye technique). In series A, 20 pigs were pretreated immediately before occlusion with either IC diltiazem (n = 5, 4 mg/2 min), IC nifedipine (n = 5, 0.4 mg/2 min), IC verapamil (n = 5, 1 mg/2 min), or isotonic sodium chloride solution (n = 5). In series B, IC diltiazem (n = 5, 4 mg/2 min), IC verapamil (n = 5, 1 mg/2 min), or isotonic saline solution (n = 5) were administered 8 minutes prior to ischemia. The IC infusion of all calcium antagonists (series A) depressed left ventricular peak pressure, diastolic blood pressure, and dp/dt max and increased heart rate and coronary venous oxygen saturation. The development of infarcts was significantly delayed by IC diltiazem and IC verapamil. Mean infarct sizes (series A) amounted to 62% in the diltiazem group, 88% in the nifedipine group, 40% in the verapamil group, and 94% in the control group. In series B, where a time period of 8 minutes elapsed between pretreatment and induction of ischemia, mean infarct sizes after 45 minutes of ischemia and 24 hours of reperfusion amounted to 47% in the diltiazem group, 4% in the verapamil group, and 76% in control experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The effect of intracoronary diltiazem on regional myocardial function and development of infarcts in porcine hearts.

The effect of intracoronary (i.c.) pretreatment with diltiazem on regional myocardial function and the development of infarcts was investigated in regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery (LAD) was distally ligated in 16 pigs for 20-90 min followed by 24 h of reperfusion. Eight pigs were treated with increasing doses of i.c. diltiazem (0.375 mg/min, 0.75 mg/min, 1 mg/min) prior to ischemia. Eight pigs served as controls. Regional myocardial function was assessed by implanted ultrasonic crystals. Infarct size was determined as ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). I.c. diltiazem mainly depressed early systolic shortening (isovolumetric contraction) and lengthening during the first half of diastole. Pretreatment with this calcium antagonist significantly delayed the development of infarcts. In control experiments, a mean infarct size of 74% was found after 45-min ischemia. At that time no infarction was observed in the treated group, where infarcts started to evolve after 60-min ischemia. It is concluded that the favorable action of i.c. diltiazem can mainly be ascribed to a reduced myocardial oxygen consumption at the onset of ischemia.

Animals↗