Biomedical subjects

R E Sievers

Publications and source records attributed to R E Sievers.

At least 37 records · Page 2Linked to original sources

PubMed1994

Is the reduction of myocardial infarct size by dietary fish oil the result of altered platelet function?

Sprague-Dawley rats fed a diet containing 12% fish oil (18% eicosapentaenoic acid [EPA] and 12% docosahexaenoic acid [DHA]), for 1 week (group I, n = 9) or 8 weeks (group III, n = 42) and controls (group II, n = 8; group IV, n = 36, respectively) were subjected to 35 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. Compared to the controls, infarct size was significantly reduced in group III (15% +/- 2%, n = 42 vs 34% +/- 4%, n = 36; p < 0.001; infarct mass/risk area x 100%), but no change in group I (39% +/- 5%, n = 9 vs 35% +/- 5%, n = 8; p = not significant). Bleeding time was prolonged in group III (290 +/- 73 sec) compared to group IV (99 +/- 10 sec, p = 0.015). Omega-3 fatty acid (EPA and DHA) levels in platelets were significantly higher in the rats fed 8 weeks of fish oil (group III) compared to the controls (group IV) and the rats fed 8 weeks of fish oil and then a regular diet until bleeding time normalized (group V) (7.2% +/- 0.6% vs 1.2% +/- 0.2% and 4.9% +/- 0.5%; 3.8% +/- 0.7% vs 1.8% +/- 0.3% and 2.8% +/- 0.6%, p < 0.001 and 0.05, respectively). These data indicate that long-term (8 weeks) dietary fish oil supplementation significantly reduces infarct size; short-term (1 week) does not. This reduction of infarct size appears to correlate with altered platelet function and EPA and DHA levels in platelets.

Animals↗

PubMed1994

Reduction of infarct size during myocardial ischemia and reperfusion by lazaroid U-74500A, a nonglucocorticoid 21-aminosteroid.

Lazaroid U-74500A, a 21-aminosteroid that inhibits iron-dependent lipid peroxidation, was previously shown to have protective effects on neuronal viability in animal models of ischemic neurologic injury. To test the hypothesis that lazaroid enhances myocardial salvage after ischemia/reperfusion, lazaroid-pretreated rats (2 mg/kg intravenously) (n = 26) and control rats pretreated with vehicle (n = 22) were subjected to 45-min left coronary (LCA) occlusion followed by 120 min of reflow. Lazaroid-pretreated rats and controls had similar ischemic risk areas (AR), as determined by phthalocyanine blue dye staining (47.2 +/- 2.3 vs. 48.2 +/- 3.0%, p = NS, mean +/- SEM). Infarct size, measured by triphenyltetrazolium staining, was markedly reduced in lazaroid-treated rats as compared with controls (6.0 +/- 1.5 vs. 22.2 +/- 3.9%, p = 0.001, infarct size/ischemic RA x 100). There were no differences in systolic blood pressure (SBP), heart rate (HR), rate-pressure product (RPP), or maximum rate of left ventricular systolic pressure development (LVdP/dt) between groups during ischemia or reperfusion. Lazaroid pretreatment enhances myocardial salvage after 45-min LCA occlusion and 2-h reflow in this animal model. This beneficial effect is independent of the hemodynamic determinants of myocardial oxygen demand.

Animals↗

PubMed1994

Effects of etidronate and lovastatin on the regression of atherosclerosis in cholesterol-fed rabbits.

Eighty New Zealand rabbits in eight groups (10 each) were fed a 0.5% cholesterol diet for 12 weeks. One group served as a control and was sacrificed at the end of 12 weeks. Seven other groups were shifted to a normal diet and received a drug(s) or placebo for the second 12 weeks. The high dose of etidronate (3 mg/kg/day) with lovastatin (6 mg/kg/day) significantly reduced the percent of aortic atherosclerotic lesions [56 +/- 21 vs. 77 +/- 17% (mean +/- SD), p < 0.05] in the regression study. Compared to the control groups for etidronate and lovastatin, the high or low dose (0.15 mg/kg/day) of etidronate significantly reduced aortic standardized plaque volume per unit (18.7 +/- 7.9 or 18.8 +/- 9.1 vs. 28.4 +/- 11.8 mm.%, p < 0.05). Lovastatin reduced pulmonary artery maximum plaque thickness (0.13 +/- 0.10 vs. 0.23 +/- 0.11 mm, p < 0.05). There were no differences in serum lipid and calcium levels in the control and treated groups. The high dose of etidronate inhibited bone mineralization as expected, whereas the low dose of etidronate did not. These data suggest that etidronate with lovastatin can regress aortic atherosclerosis in the cholesterol-fed rabbit placed on a normal diet.

Animals↗

PubMed1994

Heat-shock protein induction in rat hearts. A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection.

BACKGROUND: Previous studies have demonstrated that heat-shock treatment results in the induction of 72-kD heat-shock protein (HSP72) and a reduction of infarct size after subsequent ischemia and reperfusion. METHODS AND RESULTS: To test the hypothesis that the degree of protection from ischemic injury in heat-shocked rats correlates with the degree of prior HSP72 induction, rats pretreated with 40 degrees C, 41 degrees C, or 42 degrees C of whole-body hyperthermia followed by 24 hours of recovery and control rats (n = 6 in each group) were quantitatively assessed for the presence of myocardial HPS72 by optical densitometry of Western blots and a primary antibody that is specific for HSP72 and a tertiary antibody labeled with 125I. Although rats heat-shocked to 40 degrees C had no significant induction of myocardial HSP72, rats heat-shocked to 41 degrees C and 42 degrees C demonstrated progressively increased amounts of myocardial HSP72 compared with controls. Separate groups of rats heat-shocked to 40 degrees C (n = 16), 41 degrees C (n = 37), and 42 degrees C (n = 36) with 24 hours of recovery and controls (n = 26) were subjected to 35 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Compared with control and 40 degrees C rats, there was progressive infarct size reduction, assessed by triphenyltetrazolium chloride staining, in rats that were heat-shocked to 41 degrees C and 42 degrees C. Furthermore, there was a direct correlation between the amount of HSP72 induced and the reduction in infarct size (r = .97, P = .037). CONCLUSIONS: These results suggest that the improved salvage after heat-shock pretreatment may be related to the amount of HSP72 induced before prolonged ischemia and reperfusion.

Animals↗

PubMed1994

Exposure to environmental tobacco smoke increases myocardial infarct size in rats.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. In this study, we evaluated the influence of 3 days, 3 weeks, and 6 weeks of ETS exposure on myocardial infarct size in a rat ischemia/reperfusion model. METHODS AND RESULTS: Sprague-Dawley rats exposed to ETS (four Marlboro cigarettes per 15 minutes, 6 hours per day, 5 days per week) for 3 days (n = 24), 3 weeks (n = 21), or 6 weeks (n = 12) and control rats (n = 24, n = 21, and n = 12, respectively) were subjected to 35 minutes of left coronary artery occlusion and 2 hours of reperfusion. Infarct size and risk area were determined by triphenyltetrazolium chloride and phthalocyanine blue staining, respectively. Air nicotine, carbon monoxide, and total particulates were measured during ETS exposure. Serum lipids, plasma carbon monoxide hemoglobin (COHb), nicotine, and cotinine concentrations were measured in additional groups (6 to 13 rats each) exposed to 3 days, 3 weeks, or 6 weeks of ETS and controls. Average air nicotine, carbon monoxide, and total particulate concentrations were 1103 micrograms/m3, 92 ppm, and 60 mg/m3 for the ETS-exposed rats. Infarct size (infarct mass/risk area x 100%) increased significantly in the ETS groups compared with the control groups in a dose-dependent manner (P = .023), with longer exposure associated with larger infarct size. Infarct size nearly doubled with 6 weeks of ETS exposure (61 +/- 5% versus 34 +/- 3% for control, mean +/- SEM). Plasma COHb, nicotine, and cotinine levels increased significantly in the ETS groups in a dose-dependent manner (all P < .001). CONCLUSIONS: Exposure to passive smoking increases myocardial infarct size in a rat model of ischemia and reperfusion. This increase of infarct size exhibited a dose-response relation. These results are consistent with epidemiological studies demonstrating that ETS increases the risk of heart death.

Animals↗

PubMed1994

Metoprolol does not attenuate atherosclerosis in lipid-fed rabbits exposed to environmental tobacco smoke.

BACKGROUND: We previously demonstrated that exposure to environmental tobacco smoke (ETS) increases the development of atherosclerosis in lipid-fed rabbits. Clinical studies have suggested a protective effect of beta-blockers in smokers. Accordingly, we evaluated the effects of metoprolol in this animal model to see whether this beta-blocker would block the atherogenic effects of ETS. METHODS AND RESULTS: Thirty-two New Zealand White male rabbits on a 0.3% cholesterol diet were randomly divided into four groups: ETS-metoprolol (ETS-M), ETS-control (ETS-C), and non-ETS with metoprolol (NETS-M) and without metoprolol (NETS-C). The two metoprolol-treated groups received metoprolol at a dose of 0.4 mg.kg-1.h-1 administered subcutaneously by an osmotic pump. Rabbits in the ETS groups were exposed to sidestream smoke from four Marlboro cigarettes per 15 minutes, 6 hours a day, for 10 weeks. Average air carbon monoxide (CO), nicotine, and total particulates (TP) in the exposure chambers were 67.2 +/- 3.1 (SEM) ppm, 1133.7 +/- 78.4 micrograms/m3, and 37.7 +/- 3.0 mg/m3, respectively. Plasma nicotine was significantly higher in ETS-exposed rabbits than in nonexposed rabbits (7.1 +/- 1.9 versus 0.5 +/- 0.1 ng/mL, P < .01). Blood carbon monoxide hemoglobin (COHb) in the ETS-M group was significantly higher than that in the NETS-M group (4.0 +/- 0.2% versus 1.3 +/- 0.1%, P < .0001). The lipid lesions in the aorta and pulmonary artery were 57.2 +/- 7.6% and 33.1 +/- 6.4% (ETS-M), 62.8 +/- 8.4% and 58.4 +/- 6.1% (ETS-C), 38.7 +/- 9.4% and 24.8 +/- 7.7% (NETS-M), and 49.8 +/- 8.7% and 32.7 +/- 7.1% (NETS-C). There were significant differences in lipid deposits of the arteries between the controls and the ETS-exposed rabbits (37 +/- 1% versus 53 +/- 1%, P = .004) and between the controls and metoprolol-treated rabbits (51 +/- 1% versus 38 +/- 1%, P = .027). The benefit of metoprolol was independent of ETS exposure (ETS x metoprolol interaction, P = .595). CONCLUSIONS: Exposure to ETS significantly accelerated and metoprolol decreased the development of atherosclerosis in lipid-fed rabbits, but there was no interaction between the effects of ETS exposure and metoprolol. Metoprolol did not protect against the effects of ETS on atherosclerosis, suggesting that the beta-adrenergic system is not the mechanism of ETS-induced atherosclerosis.

Animals↗

PubMed1993

Aspirin inhibits platelet activity but does not attenuate experimental atherosclerosis.

We evaluated the antiatherosclerotic potential of aspirin, a platelet inhibitor, in lipid-fed rabbits (0.3% cholesterol diet). Seventy-five male New Zealand white rabbits were divided into treated or control groups. The treated groups were given aspirin by daily gavage for 12 weeks (1 mg/kg, 10 mg/kg, 30 mg/kg, and 60 mg/kg) and 10 rabbits served as controls. Increased bleeding time was observed in the aspirin-treated groups (average, 58 +/- 10 seconds to 75 +/- 17 seconds; p < 0.001). Only high-dose aspirin (60 mg/kg/day) significantly inhibited platelet aggregation (1.04 +/- 0.15 vs 0.67 +/- 0.14; p < 0.05). Seventeen additional rabbits had aortic endothelial injury produced by a balloon catheter. Eight of them were given aspirin (40 mg/kg/day), and the other nine served as controls. The average percent of surface lesions and lesion thickness of the aorta and pulmonary artery were not significantly reduced by aspirin. These results show that at doses that cause antiplatelet effects, aspirin does not attenuate atherosclerosis.

Analysis of Variance↗

PubMed1993

Assessment of perfused left ventricular mass in normal, ischemic, and reperfused myocardium by means of single-photon emission computed tomography of technetium-99m isonitrile.

To test the hypothesis that single-photon emission tomography of technetium (Tc) 99m hexakis 2-methoxyisobutyl isonitrile (Tc-MIBI) can accurately measure perfused left ventricular (LV) mass in nonischemic, ischemic, and reperfused myocardium, we acquired Tc-MIBI tomographic images in canines with normally perfused hearts (n = 33) after occlusion of the left anterior descending coronary artery (n = 15), after reperfusion (n = 13), and with subsequent second injection of Tc-MIBI (15 to 18 mCi; n = 12). In all ischemic studies the initial dose of Tc-MIBI (5 to 6 mCi) was injected after coronary artery occlusion but before reflow. Scintigraphic perfused LV mass was calculated from the total voxels demonstrating Tc-MIBI uptake x voxel volume (cm3) x specific gravity of myocardium (1.05 gm/cm3). After being imaged the animals were killed, the left ventricle was weighed, and the risk area was determined by dual perfusion with phthalocyanine blue dye and triphenyltetrazolium chloride (TTC). Perfused LV mass was defined as total LV mass minus the risk area mass. There was good correlation between scintigraphic and morphologic determinations of perfused left ventricular mass in nonischemic hearts (Tc-MIBI left ventricular distribution = 0.84 x left ventricular weight + .20.4, n = 33, r = 0.93, p = 0.0001) and ischemic hearts (Tc-MIBI left ventricular distribution = 0.51 x left ventricular weight + 37.9, n = 15, r = 0.83, p = 0.0001). In animals imaged both before and after reperfusion, scintigraphic determinations of the nonischemic region correlated closely (after-reflow Tc-MIBI distribution = 1.07 x before-reflow Tc-MIBI distribution--8.0, n = 13, r = 0.88, p = 0.0001), indicating that Tc-MIBI does not significantly redistribute into the ischemic zone after reperfusion. After injection of the second dose of Tc-MIBI in acutely reperfused canines, there was good correlation between the distribution mass of Tc-MIBI and the mass of viable myocardium by TTC staining (Tc-MIBI distribution = 0.61 x viable LV mass + 34.2, n = 12, r = 0.77, p = 0.0001). Furthermore, the apparent redistribution of myocardial Tc-MIBI from before and after second injection images correlated with the degree of myocardial salvage by histochemical staining (r = 0.72, p = 0.0082). In conclusion, single-photon emission computed tomography of Tc-MIBI can measure perfused LV mass accurately in both ischemic and nonischemic canine preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits.

OBJECTIVES: We evaluated the influence of passive smoking on experimental atherosclerosis in cholesterol-fed rabbits. BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. METHODS: New Zealand male rabbits were randomly divided into three groups after 2 weeks of a 0.3% cholesterol diet. Sixteen rabbits were exposed to a high and 16 rabbits to a low dose of ETS; 32 rabbits located in another room served as an unexposed control group. After 10 weeks of ETS exposure, all rabbits were killed, and the percent of aortic and pulmonary artery endothelial surfaces covered by lipid lesions was measured by staining and planimetry. RESULTS: Average air nicotine, carbon monoxide and total particulate concentrations were 1,040 micrograms/m3, 60.2 ppm and 32.8 mg/m3 for the high dose ETS group, 30 micrograms/m3, 18.8 ppm and 4.0 mg/m3 for the low dose ETS group and < 1 microgram/m3, 3.1 ppm and 0.13 mg/m3 for the control group. The percent atherosclerotic involvement of the aorta and pulmonary artery increased significantly with ETS exposure (for the aorta, 30 +/- 19% [mean +/- SD] for the control group, 36 +/- 14% for the low dose ETS group and 52 +/- 21% for the high dose ETS group, p < 0.001; for the pulmonary artery, 22 +/- 15% for the control group, 29 +/- 25% for the low dose ETS group, and 45 +/- 12% for the high dose ETS group, p < 0.001). Bleeding time was significantly shorter in the two ETS groups than in the control group (86 +/- 17 vs. 68 +/- 15, 68 +/- 18 s, p < 0.001). There were no significant differences in serum triglycerides, cholesterol and high density lipoprotein cholesterol at the end of the study. CONCLUSIONS: Environmental tobacco smoke affects platelet function and increases aortic and pulmonary artery atherosclerosis. This increase of atherosclerosis was independent of changes in serum lipids and exhibited a dose-response relation. These results are consistent with data from epidemiologic studies demonstrating that ETS increases the risk of death due to heart disease.

Analysis of Variance↗

PubMed1993

Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment.

BACKGROUND: Although previous investigators have demonstrated that myocardial preconditioning reduces infarct size, the mechanisms of cardioprotection associated with preconditioning are not completely understood. METHODS AND RESULTS: To test the hypothesis that preconditioning (four 5-minute episodes of ischemia each followed by 5 minutes of reperfusion) reduces infarct size by depleting cardiac glycogen stores and attenuating the degree of intracellular acidosis during subsequent prolonged left coronary artery occlusion, preconditioned and control rats were subjected to 45 minutes of left coronary artery occlusion and 120 minutes of reflow immediately after preconditioning (groups 1P and 1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour (groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic recovery after preconditioning but before prolonged ischemia. In each group, cardiectomy was performed in selected rats immediately before prolonged ischemia for cardiac glycogen assay. In selected animals, 31P magnetic resonance spectroscopy was performed to monitor intracellular pH and measure high-energy phosphate levels during ischemia and reperfusion. Group 1P rats demonstrated marked glycogen depletion after preconditioning compared with controls (0.72 +/- 0.39 [n = 9] versus 5.67 +/- 1.73 [n = 12] mg glucose/g wet wt; p < 0.001 versus group 1C) that was associated with attenuation of intracellular acidosis during ischemia, as measured by 31P magnetic resonance spectroscopy (6.8 +/- 0.3 [n = 11] versus 6.2 +/- 0.3 [n = 9] pH units; p < 0.01), and marked infarct size reduction (0.3 +/- 0.6% [n = 7] versus 38.1 +/- 11.3% [n = 7], infarct size divided by risk area; p < 0.0001). During ischemia, there were no differences in myocardial ATP or phosphocreatine levels or in any hemodynamic determinant of myocardial oxygen demand between groups 1P and 1C. In preconditioned rats that were allowed to recover before ischemia (groups 2P+30m, 3P+60m, and 4P+360m), the time course of glycogen repletion paralleled the loss of protection from ischemic injury. CONCLUSIONS: Glycogen depletion and the attenuation of intracellular acidosis during ischemia appear to be important factors in delaying irreversible injury and reducing infarct size in this animal model of myocardial preconditioning.

Animals↗

PubMed1992

Effect of lovastatin on suppression and regression of atherosclerosis in lipid-fed rabbits.

The present study was designed to evaluate the effects of lovastatin on suppression and regression of atherosclerosis in the lipid-fed rabbit. Fifty-seven New Zealand rabbits in six groups were fed a 0.3% cholesterol diet for 10 weeks. In the progression phase of the study, group C10 served as a control and received 1 ml of DMSO daily by gavage. Two other groups, L10 and H10, received low (L)-dose (10 mg/day) or high (H)-dose (20 mg/day) lovastatin dissolved in 1 ml of DMSO for 10 weeks. In the regression phase of the study, three groups of rabbits received the high lipid diet for 10 weeks and were then shifted to a normal diet for the second 10 weeks. During the second 10 weeks, the control group C20 received 1 ml of DMSO daily, and groups L20 and H20 received 10 and 20 mg/day of lovastatin by gavage, respectively. In the progression phase of the study, lovastatin significantly attenuated the percent of aortic lesions in groups L10 (8 +/- 7%) and H10 (9 +/- 14%) vs. the control group C10 (31 +/- 17%; p less than 0.01). There was a similar reduction in pulmonary lesions in groups L10 (10 +/- 6%) and H10 (4 +/- 5%) compared to the control group C10 (30 +/- 16%; p less than 0.01). There was also a reduction in plaque thickness in both the aorta and pulmonary artery, and hence an even greater reduction in estimated plaque volume. In the regression phase of the study, lovastatin also significantly reduced the percent of aortic lesions (groups L20 and H20 vs. C20: 27 +/- 18 and 22 +/- 7% vs. 40 +/- 17%; p less than 0.05) and pulmonary lesions (21 +/- 10 and 17 +/- 6% vs. 26 +/- 9%; p greater than 0.05 and p less than 0.05, respectively); the average maximum plaque thickness of aorta (0.24 and 0.26 mm vs. 0.49 mm; p less than 0.01); and the standardized plaque volume per unit area of aorta (4.5 and 3.4 vs. 12.1 mm-%; p less than 0.05 and p less than 0.01, respectively). However, there was no significant difference in the percent of aortic lesions between groups L20 and H20 and group C10 (27 +/- 18 and 22 +/- 7 vs. 31 +/- 17%; p greater than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Heat shock protein induction in rat hearts. A role for improved myocardial salvage after ischemia and reperfusion?

BACKGROUND: To test the hypothesis that the heat shock response is associated with improved myocardial salvage after myocardial ischemia and reperfusion, rats treated with prior whole-body hyperthermia and 24 hours of recovery (n = 26) or 20 minutes of ischemic pretreatment and 8 hours of recovery (n = 24) and control rats (n = 27, n = 24, for hyperthermic and ischemic pretreatment, respectively) were subjected to 35 minutes of left coronary artery (LCA) occlusion and 120 minutes of reperfusion. METHODS AND RESULTS: Although ventricular samples from rats subjected to either hyperthermia (n = 7) or ischemic pretreatment (n = 6) all showed induction of HSP72 (heat shock protein), Western blot analysis revealed significantly greater amounts of HSP72 in samples obtained from rats subjected to hyperthermia compared with those from rats subjected to ischemic pretreatment. Control rats (n = 7) showed no significant presence of myocardial HSP72. After 35 minutes of LCA occlusion and 2 hours of reperfusion, infarct size was significantly reduced in heat-shocked rats compared with controls (8.4 +/- 1.7%, n = 26 versus 15.5 +/- 1.9%, n = 27; p = 0.007; mean +/- SEM; infarct mass/left ventricular mass x 100). There were no significant differences in left ventricular (LV) systolic pressure, heart rate, LV dP/dt, or rate-pressure product between heat-shocked (n = 11) and control (n = 14) rats during the ischemic period. There were no differences in infarct size between ischemically pretreated and control rats subjected to 35 minutes of ischemia and reperfusion (9.7 +/- 2.1%, n = 23 versus 10.0 +/- 2.1, n = 24; p = NS). CONCLUSIONS: In this model of ischemia and reperfusion, prior heat shock was associated with significantly improved myocardial salvage after 35 minutes of LCA occlusion and reperfusion. This improved salvage was correlated with marked HSP72 induction and was independent of the hemodynamic determinants of myocardial oxygen supply and myocardial oxygen demand during the ischemic period. In contrast, mild HSP72 induction by ischemic pretreatment was not associated with improved myocardial salvage after myocardial ischemia and reperfusion. Thus, the absolute levels of HSP72 may be important in conferring protection from ischemic injury in this animal model.

Animals↗

PubMed1990

Regression of atherosclerosis in cholesterol-fed rabbits: effects of fish oil and verapamil.

Previous studies have shown that either fish oil or verapamil can attenuate the development of atherosclerosis in the lipid-fed rabbit. The present study was designed to evaluate the individual and combined effects of these two interventions on regression. Seventy New Zealand rabbits in seven groups (10 each) were fed a 0.3% cholesterol diet for 10 weeks. Control group C10 was then killed. Control group C20 was fed a 0.3% cholesterol diet and the other five groups were fed a normal diet for an additional 10 weeks. Group F in three treated groups received 2 ml/day of fish oil (Proto-Chol, eicosapentaenoic acid, 180 mg/ml and docosahexaenoic acid, 120 mg/ml) by gavage. Group V received verapamil, 2 g/1,000 ml drinking water, and group FV received both fish oil and verapamil for an additional 10 weeks. Group CF (control for fish oil) received 2 ml/day of water by gavage and group CV (control for verapamil) received water without gavage for an additional 10 weeks. The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the four control groups (C20, C10, CF and CV) was 57 +/- 22, 40 +/- 15, 40 +/- 14 and 33 +/- 25%, respectively. The fish oil or verapamil groups (F, V, FV) showed a significant reduction in aortic lesions: 15 +/- 17%, p less than 0.05; 16 +/- 12%, p less than 0.05; and 26 +/- 24%, p = NS, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

A model of acute regional myocardial ischemia and reperfusion in the rat.

Studies were conducted in 76 rats to describe and validate a new closed-chest in vivo model for acute ischemia and reperfusion of the left coronary artery. Radiolabeled microsphere distribution in six rat hearts confirmed a significant reduction in arteriolar flow at the center of the ischemic zone (93% reduction of total myocardial counts compared to nonischemic region, P less than 0.01) after 7 min of occlusion. Arteriolar flow returned to control values upon reperfusion. While hemodynamic parameters in 10 rats during 7 min of occlusion and 7 min of reperfusion were monitored, end diastolic pressures increased significantly (P less than 0.01) during occlusion. Finally, the utility of this rat model was demonstrated in a study of contrast enhanced magnetic resonance imaging (N = 4). Normal myocardium could not be differentiated from acutely ischemic myocardium on noncontrast-enhanced MR images. After 5 min of myocardial ischemia and following contrast administration (albumin-Gd-DTPA), the ischemic zone appeared less enhanced than normal myocardium. Upon release of the occluder the left ventricular free wall once again yielded a homogeneous signal similar to that of the normal myocardium.

Animals↗

PubMed1989

Acute myocardial ischemia and reperfusion: MR imaging with albumin-Gd-DTPA.

The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium.

Animals↗

PubMed1989

Assessment of myocardial salvage after ischemia and reperfusion using magnetic resonance imaging and spectroscopy.

To test the hypothesis that contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can differentiate reversible from irreversible myocardial injury, these modalities were used to study ischemia and reperfusion in a rat model. The presence of ischemia and reperfusion were confirmed with radiolabeled microspheres (n = 6). Groups of animals were subjected to either 16 (n = 17), 30 (n = 14), 60 (n = 11), or 90 (n = 14) minutes of left coronary artery (LCA) occlusion and 60 minutes reperfusion. After albumin-gadolinium (Gd)-DTPA injection, contrast-enhanced, T1-weighted, spin-echo proton images were acquired at baseline and every 16 minutes during LCA occlusion and reperfusion. In separate experiments, 31phosphorus (31P) spectra were acquired at similar time points during ischemia and reperfusion. After 16 minutes occlusion, normally perfused myocardium enhanced significantly compared with ischemic myocardium on MRI (104 +/- 7.9% vs. 61 +/- 11.0%, p less than 0.05, n = 5, mean +/- SEM, % of baseline value). MRS showed reduced phosphocreatine (PCr) and adenosine triphosphate (ATP) (58.8 +/- 2.4%, p less than or equal to 0.01; 81.4 +/- 2.4, p less than or equal to 0.01, n = 12). After 16 or 30 minutes ischemia, reflow resulted in uniform MRI signal intensity of the ischemic zone compared with normal myocardium (93.5 +/- 11.3 vs. 80.9 +/- 7.0, p = NS, n = 11, % of baseline value at 30 minutes reperfusion) and PCr recovery on MRS (94.3 +/- 4.0%, p = NS, n = 20, % baseline value at 30 minutes reflow). After 60 and 90 minutes ischemia, reflow resulted in marked enhancement of reperfused compared with normal myocardium on MRI (254.0 +/- 30.0 vs. 78.3 +/- 9.2, p less than or equal to 0.01, n = 10) and no recovery of PCr on MRS (64.1 +/- 3.0, p = NS, n = 14). Triphenyltetrazolium chloride (TTC) staining revealed transmural myocardial infarction (MI) in all hearts subjected to 60 or 90 minutes ischemia and reflow, and small nontransmural MIs in only 2/11 hearts subjected to 16 or 30 minutes ischemia and reperfusion. Thus, 1) MRI with albumin-Gd-DTPA is useful for identifying myocardial ischemia by enhancing the contrast between normally perfused and ischemic myocardia; 2) MRI with albumin-Gd-DTPA is useful for identifying reperfusion after myocardial ischemia; and 3) after reperfusion, reversible can be distinguished from irreversible myocardial injury by characteristic findings on MRI and MRS.

Albumins↗

PubMed1988

Inhibition of atherosclerosis by fish oil in cholesterol-fed rabbits.

To evaluate the effects of dietary fish oil on cholesterol-induced atherosclerosis, 36 New Zealand rabbits in four groups were fed a 0.3% cholesterol diet for 10 weeks. One group served as control, whereas groups I, II and III received 1, 2 and 3 ml/day, respectively, of fish oil (Protochol, eicosapentaenoic acid, 180 mg, and docosahexaenoic acid [DHA], 120 mg/ml). The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the control group was 59 +/- 22%. The two higher dose fish oil groups showed a significant reduction in aortic lesions: group I (40 +/- 26%, p = NS), group II (18 +/- 11%, p less than 0.01) and group III (36 +/- 22%, p less than 0.05). Area of pulmonary artery lesions was significantly higher in the control group (48 +/- 22%) as compared with group I (15 +/- 13%, p less than 0.01), group II (4 +/- 3%, p less than 0.01) and group III (8 +/- 9%, p less than 0.01). The high cholesterol diet in the control group decreased bleeding time from 82 +/- 17 to 59 +/- 22 s (p less than 0.05). Groups II and III showed an increased bleeding time (62 +/- 15 to 84 +/- 17 s and 66 +/- 22 to 95 +/- 27 s; p less than 0.05, respectively). Fish oil did not significantly alter total serum cholesterol and high density lipoprotein (HDL) cholesterol. In group II triglyceride decreased from 128 +/- 22 to 64 +/- 25 mg/dl (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Measurement of regional myocardial blood flow in dogs by ultrafast CT.

We measured blood flow within each of eight segments of the left ventricular myocardium in dogs by an Ultrafast CT scanner. The results were compared with flow determined by radiolabeled microspheres. Computed tomography (CT) flow was measured by an intravenous injection of nonionic contrast agent done simultaneously with the left atrial injection of microspheres. We calculated flow from the CT data by obtaining CT number versus time curves for regions of interest in the myocardium and by using a formula that related flow to both the time and value of the peak enhancement. Measurements were obtained in five dogs at rest and during hyperperfusion induced by chromonar. Based on 169 regional measurements, the Ultrafast CT and microsphere-determined flows correlated moderately (r = 0.68) over a range of 0.4 to 8 mL/min/g. However, when the data were divided into resting and hyperperfusion (ie, 20 to 30 minutes after the injection of the chromonar) states, a significant (P less than .001) increase in regional flow was determined from the CT measurements. The conclusion was that Ultrafast CT can distinguish between low and high myocardial flow states in dogs and has considerable potential for evaluating coronary flow reserve.

Animals↗