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Biomedical subjects

G Arnold

Publications and source records attributed to G Arnold.

At least 91 records · Page 5Linked to original sources
PubMed1996

Analysis of sequence and pathogenic properties of two variants of encephalomyocarditis virus differing in a single amino acid in VP1.

The encephalomyocarditis (EMC) virus-induced diabetes-like syndrome in mouse inbred strains was used as a model to study the insulin-dependent diabetes mellitus (IDDM). Our investigations were performed with two EMC virus variants, PV2 and PV7. After infection of SJL mice with 10(5) PFU of PV2 about 70% of the animals developed a diabetes-like syndrome, whereas the PV7 infected mice appeared healthy. Histological examination and in situ experiments revealed that the islets of Langerhans are a main target of PV2, whereas PV7 infection leads to only modest changes of the islets. Sequence analysis of both variants revealed one amino acid exchange within the capsid protein VP1. Hence, we describe the first diabetogenic and non-diabetogenic EMCV variants differing in only one single amino acid.

Amino Acid Sequence↗
PubMed1996

Cardiac efficiency during coronary occlusion and during reperfusion after emergency revascularization under cardioprotection.

Myocardial infarction in consequence of a coronary artery occlusion presents a serious problem. It is the aim of any emergency revascularization to minimize the ischemia-induced damage or to salvage reversibly injured myocardium. In experiments on 8 anesthetized pigs, myocardial protection by orthograde perfusion with a high-volume cardioplegic solution was studied under controlled conditions. The left anterior descending artery (LAD) was occluded for 60 min. Then cardiopulmonary bypass was instituted and cardioplegia induced by 8 min perfusion of Bretschneider HTK solution into the aortic root. After 15 min global ischemia, the LAD was "revascularized' and 150 min reperfusion followed. Except for the early relaxation (dP/dtmin) and mean thickening velocity in the ischemic myocardium, all variables remained essentially unchanged during LAD occlusion. During the entire reperfusion, heart rate was significantly increased compared to control: 93 +/- 23 vs. 126 +/- 20/min. Left-ventricular (LV) peak pressure was significantly decreased at the end of the reperfusion, 104 +/- 33 and 77 +/- 22 mmHg, as was dP/dtmax:2155 +/- 655 vs. 1720 +/- 895 mmHg/s. Cardiac output was insignificantly decreased at the end of reperfusion, 2.6 +/- 0.6 vs. 2.4 +/- 0.5 L/min, whereas stroke-work index exhibited a significant deterioration: 1.2 +/- 0.6 vs. 0.5 +/- 0.3 mmHg.ml/kg. LV dP/dtmin was significantly impaired after ischemia and at the end of reperfusion, -1575 +/- 385 vs. -855 +/- 310 mmHg/s, while LV end-diastolic pressure exhibited only a moderate increase: 8 +/- 5 vs. 9 +/- 3 mmHg. MVO2, in turn, remained almost constant throughout the protocol for each of two methods by which it was predicted. The results show that global work, MVO2, and external efficiency were unchanged during early and late occlusion compared to control. During the entire reperfusion the myocardium was stunned, i.e. cardiac work was decreased at maintained MVO2. Thus, external efficiency was decreased. From these results we conclude that in reperfused myocardium after cardioplegic arrest, the oxygen is only inefficiently converted to develop force.

Analysis of Variance↗
PubMed1996

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

OBJECTIVE: To amplify the description of myocardial stunning. DESIGN: Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS: 15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES: Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS: Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS: Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus.

Animals↗
PubMed1996

Analysis of respiratory water--a new method for evaluation of myocardial energy metabolism.

Aerobic ATP synthesis via oxidative phosphorylation causes a proportional production of respiratory water. Thus the amount of respiratory water produced at a given time should be a reliable measure of the current ATP demand of the mammalian myocardium. Respiratory water from isolated rabbit hearts was labeled by using the stable oxygen isotope 18O. The hearts were perfused according to the method of Langendorff (O. Langendorff. Pfluegers Arch. 61: 291-332, 1895) with 18O2-equilibrated Krebs-Henseleit solution. Control hearts were exclusively perfused with carbogen-equilibrated Krebs-Henseleit solution. Myocardial tissue was then lyophilized; the extracted water and samples from the coronary venous effluent were converted to CO2 by using the guanidine hydrochloride technique. The delta 18O values within the CO2 samples were determined by mass spectrometry and related to the standard mean ocean water (SMOW) scale. Compared with control hearts, the 18O-labeled hearts exhibited a significant increase of delta 18O values from tissue water (-47.50 +/- 0.64 vs. -40.35 +/- 2.05% SMOW; P < 0.05). The values were also significantly increased in the coronary venous effluent after a perfusion time of only 50 s (-47.50 +/- 0.64 vs. -43.66 +/- 0.91% SMOW; P < 0.05). Thus this first adaptation of the guanidine hydrochloride technique on microliter samples of myocardial tissue water and coronary venous effluent demonstrates that this method can be used to evaluate both respiratory activity and the kinetics of cardiac metabolic processes.

Adenosine Triphosphate↗
PubMed1996

Comparative steady state study with 2 fenofibrate 250 mg slow release capsules. An example of bioequivalence assessment with a highly variable drug.

Twenty healthy male volunteers were treated with 2 different oral preparations of fenofibrate according to a randomized 2-way crossover design. The test preparation was Fenofibrate 250 mg retard capsules, batch No. YXF 001, provided by MTT Medical and Technological Transfer GmbH, Unterhaching, Germany. The reference preparation was Lipanthyl 250 mg retard capsules, batch No. R9110071, manufactured by Fournier Pharma, Sulzbach, Germany. On 12 consecutive days divided in 2 periods the volunteers received 6 doses of the test and reference formulation, respectively. The daily dose of 1 capsule contained 250 mg of fenofibrate and was administered together with a standardized high calory breakfast. Blood samples were taken immediately prior to each administration and at 14 points after the last administration of each period. The concentration of the pharmacologically active compound, fenofibric acid, was determined by means of HPLC with UV detection. The calibration curve was linear in the range 0.1-20.0 micrograms/ml (r = 0.99997). A lower limit of quantification of 0.1 microgram/ml was established. The following mean values were obtained after administration of the test preparation: AUC tau 184.68 microgramsh/ml; Cmax 13.11 micrograms/ml; PTF: 125.0%. After administration of the reference formulation the following values were observed: AUC tau 175.91 microgramsh/ml, Cmax 12.27 micrograms/ml, PTF: 120.0%. AUC tau, Cmax and PTF were tested for bioequivalence parametrically after logarithmic transformation. The preparations were found to be bioequivalent.

Adult↗
PubMed1996

[Effect of a new bradycardic substance on the isolated rabbit heart].

Beside wall tension and contractility, heart rate is a major determinant of myocardial oxygen consumption. Therefore, a decrease in heart rate could prevent ischemia or reduce its consequences. We examined the effect of a new bradycardic agent of the benzazepinone-type (DK-AH 269) on eight isolated, saline-perfused rabbit hearts, bradycardia resulted from a specific blockade of i(f)-channels in sinus node cells. After control measurements (C), the substance was added in three increasing concentrations (D1: 10(-8) M, D2: 10(-7) M, D3: 10(-6) M). We observed a dose-dependent reduction in heart rate (C: 206 +/- 25, D1: 195 +/- 30, D2: 77 +/- 41, D3: 154 +/- 48/min). In the highest dosage, the duration of diastole was increased by 100%. To characterize systolic function, we measured stroke volume (SV), peak left ventricular pressure (LVPmax) and its first derivative (dP/dtmax). Aortic flow was slightly decreased whereas SV increased to 108% of control after initial reduction at the two lower dosages. LVPmax remained unchanged, and dP/dtmax was dose-dependently reduced to 91, 81, and 70% of control (C: 1885 +/- 376, D1: 1721 +/- 525, D2: 1526 +/- 504, D3: 1327 +/- 337 mm Hg/s); dP/dtmin as a measure of early relaxation was also reduced. The coronary flow per beat did not change compared with control in the presence of the two lower doses of DK-AH 269, but was significantly increased with the highest dose (C: 0.29 +/- 0.06, D1: 0.28 +/- 0.07, D2: 0.29 +/- 0.09, D3: 0.34 +/- 0.11 ml). The myocardial oxygen demand was dose-dependently decreased (C: 10.4 +/- 2.5, D1: 9.6 +/- 2.5, D2: 8.8 +/- 2.6, D3: 7.9 +/- 2.4 ml/min/100 g). The relation between subendocardial and subepicardial flow, assessed with colored microspheres, exhibited no changes in the presence of the highest dose of DK-AH 269 (C: 1.28 +/- 0.09, D3: 1.27 +/- 0.08). DK-AH 269 reduced heart rate in isolated rabbit hearts and increased the duration of diastole. Whereas systolic function was primarily left unchanged, coronary flow per beat and oxygen consumption were decreased. According to our results, this new bradycardic agent could be useful in treating coronary heart disease.

Animals↗
PubMed1995

Pretreatment with nimodipine prevents MPTP-induced neurotoxicity at the nigral, but not at the striatal level in mice.

The present study assessed the effects of pretreatment with the calcium-L-type channel blocker nimodipine on biochemical and histological parameters of systemic MPTP-induced (2 x 40 mg kg-1 body weight subcutaneously, 16 h apart), dopaminergic neurotoxicity in black C57BL/6 mice. Continuous administration of nimodipine via subcutaneously implanted pellets (10 mg), starting 7 days before administration of MPTP, did not antagonize the striatal MPTP-induced dopamine depletion (caudate-putamen: 80% of control; nucleus accumbens; 25% of control), but almost completely prevented the MPTP-induced tyrosine hydroxylase immunoreactive-cell loss in the substantia nigra (20% of control) 7 days after administration of MPTP. This data suggests that pretreatment with nimodipine--during the observation period of 7 days--protects against MPTP-induced neurotoxicity in mice at the nigral ('cell body'), but not at the synaptic striatal level.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

[Macroscopic and microscopic heart preparation in ischemic heart diseases].

The quality of the morphological analysis of myocardial and coronary alterations depends essentially on the method chosen for the heart dissection. Even if previous postmortem coronary angioplasty is not feasible, the best results are obtained by transverse sectioning of the ventricles in a bread-loaf fashion subsequent to formalin-fixation and serial cross-sectioning of the coronary arteries, with decalcification in addition if necessary. The distribution pattern of disseminated myocardial necrosis, the longitudinal, circumferential and transmural extent of infarction, its age and sequelae and its correlation to the coronary supplying areas can be evaluated with better accuracy than by dissecting the heart chambers according to the flow of blood. Cross-sectioning of coronary arteries with preservation of their luminal shape allows proper examination of the degree and extent of luminal narrowing, plaque hemorrhage, parietal and occluding thrombi and the effects and complications of angioplastic procedures or bypass surgery. Transverse sectioning of the heart is a prerequisite for adequate examination following sudden cardiac death and short-term territorial ischemia. Full-thickness samples of the ventricular walls, taken systematically with respect to coronary narrowing and coronary supplying areas, enable identification of early myocardial damage.

Coronary Disease↗
PubMed1995

Utilization of oxygen by the contractile apparatus is disturbed during reperfusion of post-ischaemic myocardium.

UNLABELLED: Post-ischaemic ventricular function remains depressed (= myocardial stunning) despite nearly normal coronary blood flow during reperfusion. In order to illuminate the causes of this phenomenon, we studied the relationship between ventricular function and myocardial oxygen consumption (MVO2tot) in experiments on 15 isolated rabbit hearts perfused with erythrocyte suspension (hct = 30%). Left ventricular systolic function was assessed by measuring aortic flow (ml.min-1), peak systolic pressure (LVPmax), dP/dtmax, and early relaxation in terms of dP/dtmin during control and 30 min after the onset of reperfusion, following 20 min global no-flow ischaemia. The pressure-volume area was calculated as a measure of total mechanical energy. The external mechanical efficiency (Eext) was assessed from stroke work and MVO2tot. Both contractile efficiency (Econ = inverse slope of the MVO2-PVA relationship) and MVO2 of the unloaded contracting heart (MVO2unl = basal MVO2 + MVO2 for excitation-contraction coupling) were calculated using pressure-volume area and MVO2tot. RESULTS: At matched heart rate (149 +/- 30 vs 147 +/- 31 min-1; mean +/- SD) and end-diastolic volume (1.3 +/- 0.2 ml), the systolic variables were significantly decreased in the stunned myocardium: aortic flow: 38 +/- 13 vs 9 +/- 11 ml.min-1, LVPmax: 112 +/- 19 vs 74 +/- 18 mmHg, and dP/dtmax: 1475 +/- 400 vs 1075 +/- 275 mmHg.s-1. Likewise, dP/dtmin was significantly impaired (-1275 +/- 250 vs -975 +/- 250). The decrease in pressure-volume area (570 +/- 280 vs 270 +/- 200 mmHg.ml.100 g-1) was not statistically significant. In contrast, both Eext (0.75 +/- 0.29 vs 0.18 +/- 0.26 arbitrary units) and Econ (31 +/- 18 vs 14 +/- 7%) were significantly decreased, whereas MVO2tot (40 +/- 9 vs 34 +/- 8 microliters.beat-1.100 g-1) and MVO2unl (26 +/- 9 vs 22 +/- 6 microliters.beat-1.100 g-1) were not. SUMMARY: Ventricular function after brief episodes of ischaemia is decreased whereas MVO2tot is maintained, i.e. external efficiency is decreased. MVO2 for the unloaded contraction remained unchanged, indicating that MVO2 for excitation-contraction coupling is inappropriately high for the depressed contractile state. The decreased contractile efficiency indicates further that O2 utilization of the contractile apparatus is disturbed during reperfusion.

Animals↗
PubMed1995

[The value of CKMB and myoglobin determinations during reperfusion after regional myocardial ischemia in the anesthesized pig].

The efficacy of a revascularization treatment after acute coronary artery occlusion can be evaluated by different diagnoses. The ECG and the time-course of, for example, the CK isoenzyme MB are widely used as quick, objective, and almost noninvasive tools. In addition, the assessment of functional recovery of the postischemic myocardium or the evaluation of the magnitude of irreversibly injured myocardium is essential for therapeutic strategies. In the present study, myoglobin that is not yet routinely established, is compared with CKMB to answer the following questions: do measurements of serum-CKMB and serum-myoglobin reliably demonstrate 1) the success of a revascularization treatment? 2) the functional recovery of the postischemic myocardium? 3) the magnitude of irreversibly injured myocardium? To answer these questions, the left anterior descending coronary arteries of 17 anesthetized pigs were occluded for 60 min and reperfused for 180 min after successful "revascularization". The major findings of this study on anesthetized pigs are: 1) The time-course of both the CKMB activity and the myoglobin concentration exhibit the successful revascularization. 2) The CKMB maximum does not exhibit the recovery of the ventricular function, whereas the myoglobin maximum moderately correlated with the contractile state (dP/dtmax) at the end of reperfusion and significantly with the recovery of dP/dtmax during reperfusion. Recovery of the regional function (= mean thickening velocity) within the 180 min reperfusion is predicted neither by CKMB nor myoglobin analysis. 3) Both investigated markers correlate closely with the magnitude of the irreversibly injured myocardium.

Animals↗
PubMed1995

Comparison between the effects of a novel Ca++ sensitizer and a phosphodiesterase inhibitor on stunned myocardium.

Inotropic agents are used widely for pharmacological bridging of the failing heart either until recovery after surgical intervention or until transplantation. EMD 57033 is a novel specific Ca++ sensitizing agent with purportedly minor phosphodiesterase (PDE) III-inhibiting properties. It acts as an inotropic agent without raising intracellular Ca++ levels. In turn, the PDE III-inhibitor enoximone has been used for several years to treat low cardiac output syndrome. However, little is known about its effects on postischemic reperfused (stunned) myocardium. We investigated the effects of EMD 57033 (EMD; 30 microM) and enoximone (E20 micrograms/ml) on stunned myocardium. The experiments were performed on 16 isolated rabbit hearts perfused with an erythrocyte suspension (hematocrit = 30%; [Ca++] = 2.5 mM). Hearts were reperfused after a 20 min no-flow ischemia. Measurements were performed at control, 30 min after the onset of reperfusion, and after administration of one of the drugs. Both agents significantly improved the depressed systolic function [left ventricular pressure (LVP)max from 61 +/- 12 to 93 +/- 18 mmHg, and its derived pressure (dP/dt)max from 860 +/- 220 to 1340 +/- 300 mmHg/s and LVPmax from 78 +/- 9 to 83 +/- 15 mmHg, and its derivative dP/dtmax from 1040 +/- 230 to 1385 +/- 300 mmHg/s, respectively] and early relaxation (dP/dtmin from 810 +/- 250 to 1260 +/- 345 mmHg/s and from 1000 +/- 200 to 1135 +/- 295 mmHg/s, respectively) that occurred during postischemic reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Minimal interval length for safe determination of brief heart rate variability].

UNLABELLED: After heart rate variability (HRV) had been established in the clinic, the question about the minimum interval length for analyzing electrocardiograms emerged. Respiration rate, heart rate and heart rate variability were analyzed in 25 sport divers during 6 min intervals at control, immersion, submersion and while SCUBA diving. Thereafter, the interval length was systematically shortened to 1 min. RESULTS: Respiration rate was significantly reduced during submersion and diving. Heart rate, in turn, remained essentially unchanged during the four experimental steps. The HRV measures in the time domain (standard deviation, coefficient of variation, RMSSD and pNN50) exhibited significant changes during immersion, submersion and diving compared to control conditions. The spectral density in the low frequency range was increased compared to control, the increase being significant during diving. Immersion, submersion and diving, thus, present strong stimuli for the autonomic nervous system. The length of the HRV measures of the time domain could be shortened to 3 min without significant loss of information, except for pNN50. Reduction of the respiration rate during diving considerably shifted the respiratory arrhythmia from the high to the low frequency range. Such shifts deserve special attention interpreting HRV measures from the frequency domain. The interval length for the measures in the frequency domain could only be shortened to 5 min. CONCLUSION: Measures from the time domain, in particular standard deviation and co-efficient of variation, seem to be superior to measures from the frequency domain in analyzing short-term HRV.

Adult↗
PubMed1995

Epidemiological, genetic, pharmacological, kinesiological, nuclear medical (IBZM-SPECT), standard and functional MRI studies on Parkinson's disease and related disorders and economic evaluation of Parkinson's disease therapy--clinical projects in the BMFT-research program Munich: "Parkinson's disease and other basal ganglia disorders".

The results of selected clinical research projects related to epidemiological, genetic, pharmacological, kinesiological, and neuroimaging aspects (SPECT, PET, MRI, functional MRI) of basal ganglia disorders such as Parkinson's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and Wilson's disease are summarized. A retrospective pharmacoeconomic analysis of Parkinson's disease is presented. These studies are part of a nationwide research program of the German ministry of research and technology (BMFT) entitled "Parkinson's disease and other basal ganglia disorders" and were carried out at the Department of Neurology, LMU München.

Basal Ganglia Diseases↗
PubMed1994

Clinical progressive supranuclear palsy: differential diagnosis by IBZM-SPECT and MRI.

In order to in vivo identify subgroups in eight patients with the clinical diagnosis of progressive supranuclear palsy (PSP), we have performed 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT), a nuclear medicine technique, to visualize dopamine D2 receptors in vivo, and high resolution (TE/TR 2900/20-90) magnetic resonance imaging (MRI) to evaluate morphological CNS changes. All patients exhibited similar clinical features including supranuclear vertical gaze palsy, especially of downward gaze, predominantly axial rigidity especially in the neck, bradykinesia, instability of balance with easy falls, and poor response to dopaminergic drugs. Specific striatal dopamine D2 receptor binding in IBZM-SPECT, as calculated by a basal ganglia to frontal cortex ratio (BG/FC) was reduced in 5 patients, but normal in 3 patients. In MRI, these 3 patients exhibited multiple hyperintense white matter lesions; 2 of them had no midbrain atrophy. In contrast, all 5 patients with reduced IBZM binding lacked multiple white matter lesions in MRI, but 4 of them showed marked midbrain atrophy. This pilot study with IBZM-SPECT for in vivo imaging of striatal dopamine D2 receptors and T2-weighted MRI supports published neuropathological findings that clinical signs of PSP appeared to be due to heterogeneous neuropathology.

Aged↗
PubMed1993

The inhibition of HIV-1 protease by interface peptides.

Previous studies have shown that some peptides derived from one of the terminal amino acid segments of the homodimeric HIV-1 protease show moderate inhibition of this enzyme probably by interfering with the "interface" structure formed by the four terminal segments of the dimer. Different peptides, with improved inhibitory potency, were devised by computer modelling, synthesized, and tested. Ac-TVSFNF, the short peptide with the best inhibition so far (IC50 = 80 microM) is identical with the C-terminal part of the gag-pol frame shift protein p6*. This suggests a regulatory function of p6* as a dimerization inhibitor of HIV protease in the virion. Peptides derived from the active site sequence of PR are inactive. The two terminal hexapeptides of reverse transcriptase are also inactive in the HIV-1 PR activity assay.

Amino Acid Sequence↗
PubMed1993

A unique scenario for coronary atherectomy.

Despite several attempts, balloon angioplasty of a slightly eccentric stenotic lesion in the proximal right coronary artery failed to result in any increase of luminal diameter. Following disruption and partial removal of a fibrous atherosclerotic cap using directional atherectomy, subsequent balloon angioplasty was highly successful.

Angioplasty, Balloon, Coronary↗
PubMed1993

Outbred mice infected by an encephalomyocarditis virus variant: a model for studying chronic viral heart disease.

Male 8 to 20-week-old NMRI mice (an outbred strain) infected with the encephalomyocarditis virus (EMCV) plaque variant (PV) 7 consistently develop a distinct myocarditis with a relatively low mortality (21%). Myocarditis occurs in essence independent of the virus dose applied, and other internal organs are not affected. Nevertheless, 3.5-week-old NMRI mice perished within 5 days of virus inoculation and exhibited disseminated myofibrillar degeneration (MFD); this obviously virus-induced myocardial damage was accompanied by scanty inflammatory infiltrates. EMCV PV7 infection of adult male C57Bl/6 and DBA/2 mice causes myocarditis comparable to that seen in NMRI mice. In DBA/2 mice, however, the virus-induced myocardial necrosis is complicated by subtotal calcification. This strain has a genetically determined "spontaneous" calcification of the myocardium, as shown by the study of uninfected controls. EMCV PV7-infected NMRI mice appear a promising model for study of long-term effects of viral myocarditis, possibly including cardiomyopathy. Furthermore, this outbred mouse strain offers the possibility of examining the pathogenesis of direct viral cytolysis and its relation to MFD as well as immunologically mediated cell damage.

Age Factors↗