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Biomedical subjects

L Whitesell

Publications and source records attributed to L Whitesell.

48 records · Page 3Linked to original sources
PubMed1990

Coronary hyperperfusion and ventricular function in intact and isovolumic pig hearts.

This study characterized the effect of coronary hyperperfusion on left ventricular (LV) geometry and myocardial vascular and tissue volumes in intact hearts, and tested the hypothesis that ventricular function is significantly enhanced only under isovolumic conditions. Randomized 10-min trials of coronary perfusion pressures at approximately 100-110, approximately 150-160, and approximately 180-190 mmHg were performed in extracorporeally perfused pig hearts. First, ultrasonic crystals were used to measure LV wall thickness and major and minor epicardial diameters. LV pressures, maximum dP/dt, and myocardial O2 consumption were not significantly different despite increases in the end-diastolic and end-systolic wall thickness. There were either no changes or small decreases in epicardial major and minor axis dimensions. Second, intramyocardial small vessel vascular and extracellular volumes were measured using radiolabeled dextran and inulin. There was no significant difference in small vessel plasma volume or extracellular space. Finally, pigs were placed on cardiopulmonary bypass and LV volume was fixed with a ventricular balloon. In this isovolumic preparation, coronary hyperperfusion significantly increased peak LV pressure. We conclude that coronary hyperperfusion in hearts with intact peripheral circulations results in small changes in LV geometry but no physiologically significant changes in LV performance. Only under the rigid conditions of an isovolumic preparation is LV function enhanced, and thus the "garden-hose" effect is a model-dependent phenomenon.

Animals↗
PubMed1989

Phasic pressures and diameters in small epicardial veins of the unrestrained heart.

Previous data from this laboratory have revealed a large pressure pulse in small veins on the epicardial surface of the right ventricle of the rabbit. The phasic relationship between venule pressures and venule diameters in a beating heart was examined. Luminal pressures were measured in 39 different veins on the epicardial surface of the rabbit right ventricle. The venous luminal pressures averaged 12.6 mmHg maximum and 1.0 mmHg minimum. Pressures in 23 different small veins were also obtained at different right ventricular afterloads. Peak venous pressures increased with peak right ventricular pressure. The phasic diameter changes of 119 different vessels were examined. Vessel diameters decreased as luminal pressures increased. The average change in vessel diameter through a cardiac cycle was 20%, with a range from 0 to 60%. The large pulse pressures found in small veins appear to be related to decreasing vessel diameters and probably result from the displacement of blood as the vessels narrow.

Animals↗
PubMed1985

Effect of diltiazem and ibuprofen on right ventricular hypertrophy in an experimental model of hypoxic pulmonary hypertension.

The effectiveness of diltiazem, a slow channel calcium blocker, ibuprofen, a nonselective inhibitor of prostanoid synthesis, and the selective inhibition of thromboxane A2 with imidazole and UK-38,485 in retarding the development of right ventricular (RV) hypertrophy was assessed in a rat model of chronic hypoxic pulmonary hypertension. Both ibuprofen and diltiazem significantly reduced RV hypertrophy in the chronically hypoxic rat. In contrast, selective inhibition of thromboxane A2 was ineffective in reducing RV hypertrophy. The beneficial effect of ibuprofen was unrelated to inhibition of thromboxane A2. Furthermore, thromboxane A2 did not appear to be involved in the development of RV hypertrophy in this experimental model of hypoxic pulmonary hypertension.

Animals↗
PubMed1985

Coronary artery spasm after abrupt withdrawal of nitroglycerin in rabbits.

The potential for abrupt withdrawal of nitroglycerin (NTG) to create coronary artery spasm was assessed in New Zealand white rabbits. In the control setting, electrocardiograms were taken from 7 anesthetized rabbits. The administration of intravenous ergonovine did not provoke ST-segment shifts or arrhythmias. Two inches of topical NTG (2%) was applied 3 times daily to a shaved area on the back of each rabbit over a 6-week period. Forty hours after abrupt withdrawal of NTG, intravenous ergonovine and indomethacin were given. Six of 7 rabbits had electrocardiographic changes: ventricular tachycardia in 2, ventricular fibrillation in 1, and significant (1 mm or more) ST-segment shifts in 5 rabbits. Three rabbits died. Sixty-four hours after NTG administration the remaining 4 rabbits were reexamined. One had baseline electrocardiographic evidence of severe myocardial ischemia. Repeat ergonovine and indomethacin testing in the others revealed ventricular tachycardia progressing to asystole in 1, premature ventricular complexes in 1, and ST-segment elevation in another. Two of the remaining 4 rabbits died. Eighty-two hours after NTG administration the remaining 2 rabbits were found dead in their cages. Nitroblue tetrazolium studies revealed extensive myocardial infarction in both animals. Additional studies were performed in 10 normal rabbits. Neither ergonovine nor indomethacin induced ST-segment shifts or arrhythmias in this control population.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The release of thromboxane A2 and prostacyclin following experimental acute pulmonary embolism.

The contributions of thromboxane A2 (TXA2) and prostacyclin (PGI2) to the effects of acute pulmonary embolism were evaluated in 18 open-chest rabbits. All rabbits received autologous whole-blood-clot embolus (.4 cc) by way of a catheter in the right ventricle. Pulmonary artery (PA) and left atrial (LA) pressures, and aortic flow (AOQ) were recorded. The stable metabolites of TXA2 (TXB2) and PGI2 (6-Keto PGF1) were assayed by radioimmunoassay at pre- and post-embolization periods (+5, +10, +20, +30, and +40 minutes). Significant elevations of pulmonary vascular resistance (PVR) (normalized), PA pressure, and reduction of AOQ were noted comparing pre-embolus to +5 minute time intervals. A negative correlation was reached between PGI2 and AOQ at +40 minutes (p less than .05). Five of the 13 rabbits died prematurely. At +5 minutes these 5 rabbits had higher PVR (p less than .001) and lower AOQ (p less than .01) than their living counterparts. At +10 minutes AOQ was still significantly lower (p less than .005) and TXB2 was higher (p less than .05) in the premature death group. We conclude that TXB2 is significantly but transiently elevated early following acute pulmonary embolism and may contribute to mortality. In contrast PGI2 does not appear to play an immediate role in the hemodynamic events following embolization but does rise to significant levels later in the course possibly in an attempt to compensate for reduced flow.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease.

The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease.

Animals↗
PubMed1981

Radionuclide imaging of experimental myocarditis.

The ability of 67Ga citrate and 99mTc pyrophosphate cardiac imaging to detect myocarditis was assessed in an experimental rabbit model. Twenty-three rabbits were imaged approximately 72 hours after infusion of i.v. norepinephrine. Diffuse cardiac uptake was found in 13 of 15 rabbits scanned with 67Ga. Tissue distribution studies documented significant myocardial uptake of 67Ga in those with positive scans. Precordial imaging and tissue distribution studies revealed no cardiac uptake in the eight rabbits scanned with 99mTc. Histologic examination of all 23 hearts revealed qualitatively similar, typical lesions of myocarditis. This study suggests that cardiac imaging with 67Ga may be useful in the detection of myocarditis.

Animals↗
PubMed1981

Adhesive properties of MDCK cell membranes possible role in epithelial histogenesis.

MDCK cells in culture form a functional transporting epithelium. Apical surface of MDCK monolayers are not adhesive to free MDCK cells that fail to grow attached to existing monolayers. In contrast, when plated at high density (106 cm-2) MDCK cells form multilayered structures in which only the outermost layer shows a typical apical surface (microvilli, tight junctions, etc). In the lower layers cell-cell contacts (desmosomes, etc) are made, suggesting that the basolateral surfaces remain adhesive. Using a novel, quantitative, heterotypic cell adhesion reaction with aged human red cells, were have measured the adhesive properties of the apical surfaces of MDCK cells in a variety of conditions. It is found that the adhesion of red cells is dependent on cell density in the monolayer and falls to a low value at confluence. The reaction is considerably stronger at 6 degrees C compared to 22 degrees C (the temperature of most studies), while at 37 degrees C the reaction is expressed less strongly. MDCK cells with adherent red cells fail to divide, suggesting that the cell surface fluence. The expression of the adhesive property is associated with cell division. This was shown by inducing synchrony in cultures either by refeeding starved cultures or by removal of a thymidine " block". Peaks in adhesiveness were related to peaks in thymidine incorporation in synchronized cultures. Because of the precise quantitative way in which adhesion can be measured it is considered that this is an ideal system in which to identify the membrane components responsible for the reaction. Furthermore, it may prove possible to identify signals that arise as an immediate consequence of the adhesion reaction.

Animals↗
PubMed1980

Early corticosteroid administration in experimental radiation-induced heart disease.

The ability of dexamethasone (DEX) to reduce the severity of the late stage of radiation-induced heart disease (RIHD) was assessed in 25 New Zealand white rabbits. Ten rabbits served as unirradiated controls (CONT). In Group A, seven rabbits received intravenous DEX prior to irradiation and every 24 hours for three consecutive days. DEX was not administered to the eight rabbits in Group B. At 100 days postirradiation, the severity of the late state was determined by microscopic examination (MICRO) for myocardial fibrosis and determination of myocardial hydroxyproline content (MHP). Myocardial fibrosis was evident in Groups A (40%) and B (80%) while none was present in CONT by MICRO. One rabbit in Group B with no fibrosis by MICRO had abnormally increased MHP. MHP was significantly increased in Groups A and B, as compared to CONT (p less than 0.01). In addition to less fibrosis by MICRO, Group A demonstrated a significant reduction of MHP when compared to Group B (p less than 0.05). Determination of MHP may be superior to MICRO in the detection of the late stage of RIHD. Also, early DEX administration appears to reduce myocardial collagen content (fibrosis) in this experimental model.

Animals↗
PubMedDate not supplied

Detection of functional interferon alpha receptors in human neuroendocrine tumor cell lines using a new monoclonal antibody.

While first described as antiviral agents, interferons (IFNs) exhibit significant antiproliferative and antitumor effects as well. IFN alpha has been successfully used in clinical trials to treat several malignancies, including leukemias and certain solid tumors. While many cell types have been studied for IFN alpha receptor expression, very little is known about receptor expression on human neuroendocrine cells. Using a novel anti-IFN alpha receptor monoclonal antibody, we examined IFN alpha receptor expression in 10 human cell lines derived from tumors of neuroendocrine origin, including neuroblastoma, neuroepithelioma and small cell lung carcinoma. All cell lines studied displayed a similar pattern of IFN alpha receptor expression and 5 of 8 cell lines demonstrated reduced thymidine incorporation following IFN alpha treatment. Addition of exogenous IFN alpha caused a decrease in IFN alpha receptor expression, while differentiating agents, such as phorbol esters and retinoic acid, induced an increase in receptor number without altering receptor affinity.

Antibodies, Monoclonal↗