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Biomedical subjects

R E Sievers

Publications and source records attributed to R E Sievers.

At least 19 recordsLinked to original sources
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↗
PubMed1987

Gas chromatographic measurement of carbon monoxide in hydrocarbon matrices with a redox chemiluminescence detector.

The rapid measurement of trace levels of carbon monoxide in ethylene by gas chromatography with redox chemiluminescence detection is described. Linear response for carbon monoxide over three decades and a detection limit in the sub-parts per million by volume (ppmv) concentration range were observed without methanation or preconcentration of the sample. Samples containing 0.2 ppmv of carbon monoxide in ethylene were readily quantitated.

Carbon Monoxide↗
PubMed1987

Verapamil and diet halt progression of atherosclerosis in cholesterol fed rabbits.

The present study was designed to evaluate the effects of oral verapamil and normal diet on regression of atherosclerotic plaque in cholesterol fed rabbits. Forty-three rabbits were separated into 6 groups and studied for 24 weeks. All groups had a cholesterol diet for the first 12 weeks. Group I was then sacrificed and had 38 +/- 23% (mean +/- standard deviation) aortic plaque. During weeks 13 to 24, group II (cholesterol diet) and group III (normal diet) had similar percentages of aortic plaque: 80 +/- 7% and 78 +/- 22%, respectively. Group IV (cholesterol diet), was treated with oral verapamil for 24 weeks and had significantly less plaque (54 +/- 10%) than group II, (80 +/- 7%). In group V (cholesterol diet), treatment with oral verapamil during weeks 13 to 24 did not significantly reduce plaque (70 +/- 23%), compared to group II, (80 +/- 7%). In group VI, normal diet and verapamil during weeks 13 to 24 significantly reduced aortic plaque (46 +/- 25) when compared to group II (80 +/- 7%). Group VI (46%) did not differ from group I (38%). It is concluded that verapamil combined with a normalized diet can halt the progression of aortic atherosclerosis after a 12 week atherogenic diet in rabbits. Verapamil or diet alone was ineffective in the second 12 weeks. Overall, verapamil was effective in preventing atherosclerosis but was ineffective in causing regression of atherosclerosis.

Animals↗
PubMed1987

Lactate accumulation in ischemic- and anoxic-isolated rat hearts assessed by H-1 spectroscopy.

Proton magnetic resonance (MR) spectroscopy with homonuclear editing was used to assess lactate accumulation in ischemic and anoxic hearts perfused according to the Langendorff method. An increase in the lactate signal was observed after 5 minutes of ischemia and after 10 to 20 minutes of anoxia. This study demonstrates that proton MR spectroscopy can be used to monitor the time course of MR-visible lactate levels in ischemic and anoxic isolated rat hearts.

Animals↗
PubMed1984

Chromatographic analysis of organic compounds in the atmosphere.

Fused silica capillary columns with thick films of cross-linked coatings have been used to separate many of the organic compounds that are present in the volatile fraction of automobile exhaust and in ambient air. Techniques have been developed that allow reversible collection and pre-concentration of organic compounds in ambient air on polymeric sorbents with minimal artifacts. The exhaust samples, which are directly injected without pre-concentration on sorbents, contain many of the same organic compounds that are found in sorbent-collected samples of urban ambient air. Similar anthropogenic organic compounds are not, in general, detected (less than 0.02 ppbV) in air samples from remote, rural areas in Colorado.

Air↗
PubMed1984

Direct pharmacologic and osmolal effects of contrast media on the mechanics of heart muscle isolated from cats.

We studied 56 right ventricular papillary muscles isolated from cats to determine whether the direct mechanical effects of contrast media are due to their pharmacologic action or to the hyperosmolality caused by them. A 10% solution of Renografin-76 abruptly decreased force 22% below control, then slowly increased it to 22% above control. To elucidate these changes we also studied: (1) Renografin-60 (lower concentration of diatrizoate); (2) meglumine and diatrizoate; (3) meglumine alone; (4) diatrizoate sodium; (5) ethylene diamine tetra-acetic acid (EDTA) (same concentration as in Renografin-76); (6) sucrose to increase osmolality; and (7) Amipaque (metrizamide), a contrast medium without meglumine or diatrizoate. All solutions containing meglumine, and EDTA alone decreased force. Diatrizoate sodium also decreased force initially, presumably due to the high sodium concentration. Meglumine alone decreased force abruptly and substantially. In contrast, metrizamide and 100 mmol sucrose only increased force. Thus, the abrupt decrease in force was caused by the pharmacologic action of meglumine, EDTA, or high sodium in the contrast media, whereas the slow increase in force was caused by hyperosmolality.

Animals↗
PubMed1984

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs.

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Animals↗
PubMed1983

Influence of atrial systole on the Frank-Starling relation and the end-diastolic pressure-diameter relation of the left ventricle.

The influence of atrial systole on the left ventricular function curve (stroke volume vs end-diastolic pressure or end-diastolic diameter) and on the left ventricular end-diastolic pressure diameter relation was studied in nine anesthetized, open-chest dogs whose atrioventricular (AV) node had been completely blocked. Measurements were made during volume loading with the pericardium closed and opened and during alternate AV sequential pacing (to permit atrial contribution to ventricular filling) and AV simultaneous pacing (to prevent atrial contribution). When the pericardium was closed, withdrawal of the atrial contribution shifted the stroke-volume end-diastolic pressure relation downward, but did not shift the stroke volume-end-diastolic diameter relation, i.e., it reduced stroke volume for a given end-diastolic pressure according to a reduction in end-diastolic volume. The downward shift of the stroke volume-end-diastolic pressure relation was caused by an upward shift of the end-diastolic pressure-diameter relation, which, for a given end-diastolic pressure, resulted in a smaller end-diastolic diameter and, thus, in a smaller stroke volume. The reason for the upward shift in the end-diastolic pressure-diameter relation was that the atrium remained full and thus increased pericardial pressure by increasing pericardial volume. Opening the pericardium shifted the end-diastolic pressure-diameter relation downward and to the right, shifted the stroke volume-end-diastolic diameter relation upward and abolished the effect of withdrawal of the atrial contribution on these curves. We conclude that in the presence of an intact pericardium, atrial systole shifts the stroke volume-end-diastolic pressure relation because it shifts the end-diastolic pressure-diameter relation and it improves left ventricular performance by increasing preload.

Animals↗
PubMed1982

Measurement of coronary sinus blood flow by fiber-optic laser Doppler anemometry.

The Doppler shift of a laser has been used to measure the velocity of blood in the coronary sinus of the dog. The laser was delivered along a fine fiber-optic probe, which was also used to receive the reflected light. The Doppler shift was measured from the output of a digital spectrum analyzer. This measurement, proportional to the velocity of blood, was correlated with the blood flow measured by an electromagnetic flowmeter. Studies were performed on 112 successful maneuvers in eight consecutive anesthetized dogs. In the minimally damped electromagnetic flow traces, the correlation between coronary sinus blood flow velocity and coronary sinus blood flow was high (r greater than 0.95). This measurement will give absolute flow values only if the exact dimensions of the coronary sinus are known. The linear relationship of coronary sinus velocity and flow supports the postulate that coronary sinus dimension remains similar during normal and high flows. This technique, fiber-optic laser Doppler anemometry, is an accurate measure of relative coronary sinus blood flow. It is suitable for use in human coronary sinuses, especially to monitor the effect of interventions.

Animals↗
PubMed1982

Verapamil preserves myocardial contractility in the hereditary cardiomyopathy of the Syrian hamster.

We attempted to alter the inherited myocardial damage and loss of contractility of the cardiomyopathic Syrian hamster (strain U-MX7-1) by giving cardiac drugs that altered intracellular calcium and myocardial workload. Thirty-seven 21-day-old cardiomyopathic and thirty-seven 21-day-old normal hamsters were divided into five groups each: verapamil-, propranolol-, digoxin-, hydralazine-, and saline-injected. On their 90th day of life, the hamsters were killed. Of the five cardiomyopathic groups, only verapamil reduced myocardial damage. When both "control" and cardiomyopathic hamsters were treated with saline, digoxin, or propranolol, the cardiomyopathic hamsters had significantly less contractile force, maximal rate of force development, and maximum velocity of unloaded shortening. When both groups were treated with verapamil or hydralazine, there were no significant group differences in the indices of contractility. However, when saline-treated cardiomyopathic hamsters were compared with drug-treated cardiomyopathic hamsters, only verapamil preserved myocardial contractility. There was also a weak correlation between the Vmax and the actin-activated ATPase activity of the cardiomyopathic hamsters (r = 0.63, P less than 0.001). We conclude that verapamil helped protect the myocardium of genetically cardiomyopathic hamsters against structural damage, and helped preserve myocardial contractility.

Actins↗