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J C Keith

Publications and source records attributed to J C Keith.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cardiac ultrastructure and electrocardiogram of the short-tailed shrew, Blarina brevicauda.

The smaller species of shrews have been of considerable interest to scientists because of their high rate of metabolism, structure-functional and behavioral adaptations to support their energy demands. The present data are the first detailed cardiac ultrastructural findings and electrocardiographic (ECG) data of adult and immature small short-tailed shrews, Blarina brevicauda. The heart is morphologically elongated and heart rates in excess of 900 b/min were observed, but ECG components and pattern are non-distinctive for this species. Ultrastructurally, the sarcomeres, tubular and sarcotubular systems and Purkinje cells resemble closely those observed in larger, less active mammals. Several distinctive features resembling those seen in some other shrews or hummingbirds exist, including reduced quantities of myocyte glycogen, irregularly shaped and tightly packed mitochondria, increased neural and vascular elements in the myocardium, and small size and unusual dispersion of atrial specific granules. These morphologic findings suggest that the remarkable physiologic performance of the heart of Blarina brevicauda is supported by a combination of macroscopic, histologic and cellular adaptations.

Animals↗
PubMed1992

Thromboxane synthetase inhibition produces maternal and fetal vasodilation during ovine pregnancy-induced hypertension: a Doppler flow velocimetric study.

Changes in maternal and fetal umbilical arterial vasoreactivity during ovine pregnancy-induced hypertension and following intravenous administration of CGS 12970 [3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid] were assessed. Continuous wave Doppler flow velocimetry was used to assess vascular reactivity during normotensive baseline, during ovine pregnancy-induced hypertension triggered by a 72-hour fast, and following thromboxane synthetase inhibition with CGS 12970. Uterine and umbilical arterial systolic/diastolic flow ratios increased significantly with the onset of sustained hypertension. After thromboxane synthetase inhibition, uterine and umbilical artery systolic/diastolic flow ratios were not different from baseline, and maternal blood pressure had returned to baseline values. These data indicate that thromboxane produces maternal and fetal vasoconstriction during ovine pregnancy-induced hypertension. Furthermore, these data provide strong evidence that thromboxane synthetase inhibition allows vasodilation, resulting in improved maternal and fetal condition.

Animals↗
PubMed1990

Naturally occurring cardiomyopathy in the Doberman pinscher: a possible large animal model of human cardiomyopathy?

Currently there is no large animal model of dilated cardiomyopathy. The smaller animal models of cardiomyopathy, such as the Syrian hamster, cannot be studied with echocardiography and cardiac catheterization, and the relevance of these models to human dilated cardiomyopathy is open to question. On the basis of some initial observations in Doberman pinschers, it was speculated that these dogs could have occult left ventricular dysfunction. Accordingly, studies were performed in 46 apparently healthy Doberman pinschers and in 41 mongrel dogs: two-dimensional echocardiography (30 dogs in each group), cardiac catheterization (16 Doberman pinschers and 12 mongrels) and coronary blood flow studies (13 Doberman pinschers and 6 mongrels). In the awake, unsedated dogs studied with echocardiography, left ventricular wall thickening was significantly less in the Dobermans than in the mongrels (28% versus 36%, p = 0.0003). In the anesthetized dogs undergoing cardiac catheterization, left ventricular ejection fraction was significantly lower in the Dobermans than in the mongrels (0.38 versus 0.63, p = 0.0001). Rest coronary blood flow and coronary blood flow reserve were similar in the two groups. It is concluded that apparently healthy Doberman pinschers have occult left ventricular dysfunction. These dogs may serve as a large animal model of dilated cardiomyopathy and should not be used experimentally to study normal cardiac physiology.

Animals↗
PubMed1989

Effects of thromboxane synthetase inhibition on maternal-fetal homeostasis in gravid ewes with ovine pregnancy-induced hypertension.

Simultaneous maternal indirect blood pressure measurements, electronic fetal heart rate monitoring, and ultrasonographic biophysical profile testing were used to assess maternal-fetal homeostasis in gravid ewes during gestational days 127 to 134 (term 146), during a 72-hour fast, and during treatment with thromboxane synthetase inhibitors CGS13080 and CGS12970. Seventy-five percent of the ewes (12 of 16) developed clinical signs of ovine pregnancy-induced hypertension, including maternal hypertension and fetal depression. In three untreated hypertensive ewes, pregnancy was terminated by spontaneous premature delivery, and one maternal death occurred after an eclamptic seizure. All nine ewes treated with one of the two thromboxane synthetase inhibitors responded to therapy with decreases in blood pressure and resolution of fetal depression. These nine ewes completed gestation, and were delivered at term. These data indicate that therapy with thromboxane synthetase inhibitors in this animal model of preeclampsia results in profoundly beneficial effects and suggest that further studies of thromboxane synthetase inhibitors are warranted in preeclampsia.

Animals↗
PubMed1989

Gastric and cardiac organoprotection by lidocaine.

The concept of cytoprotection has been applied to many tissues afforded protection by drugs or endogenous chemicals against organelle, cyto- or histopathologic damage. We review here the "organoprotection" by lidocaine in rats and dogs as appraised by in vitro, ex vivo, and in vivo experiments with the stomach and heart, and as revealed at organelle to organ functional levels. Gastric mucosal lesions induced by 80% ethanol with 100 mM HCl on the ex vivo rat stomach were significantly reduced by lidocaine (2.2-4.4 mg/kg bolus followed by 66-132 micrograms/kg/min i. v. infusion). In anesthetized dogs with gastric corporeal lesions induced by increased gastric intraluminal pressure (50 mm Hg, 2.5 hrs), lidocaine (2.2 mg/kg bolus plus 66 micrograms/kg/min infusion) significantly reduced lesion severity. In the isolated rat heart, reperfusion after a 60 min period of ischemia induced localized cardiac mitochondrial swelling and disruption in ventricular apices which was greatly reduced if hearts were pretreated (15 min perfusion with lidocaine). In intact rats subjected to hemorrhagic shock, lidocaine pretreatment also facilitated shock resuscitation and reduced ultrastructural damage. In these diverse experiments, lidocaine organoprotection was likely mediated in part through reduction of ischemia induced organelle membrane damage and through reduction of reperfusion-induced superoxide and other oxygen-derived free radical related damage.

Animals↗
PubMed1988

Effect of thromboxane synthetase inhibition on platelet function and morphology during ovine pregnancy-induced hypertension.

Arterial blood pressure, serum fibrin/fibrinogen degratory products, plasma thromboxane B2, in vitro platelet aggregation, and platelet ultrastructure were studied in ten gravid ewes during fast-triggered ovine pregnancy-induced hypertension and subsequent administration of the thromboxane synthetase inhibitors CGS13080 and CGS12970. During the hypertensive period, blood pressure (p less than 0.005) and plasma thromboxane B2 levels (p less than 0.005) were significantly altered. Collagen-induced in vitro platelet aggregation lag times increased (p less than 0.01), and percent aggregation (p less than 0.05), primary (p less than 0.01), and secondary (p less than 0.005) aggregatory slopes decreased. Collagen also failed to induce aggregation in some ewes. Primary slopes of ADP-induced in vitro platelet aggregation decreased (p less than 0.01) during hypertension. Degranulation and open canalicular tubule system swelling were observed in platelets which produced abnormal or no aggregation response. However, these ultrastructural abnormalities did not necessarily correspond to hypertensive periods. Thromboxane synthetase inhibitor administration lowered blood pressure (p less than 0.005) and plasma thromboxane B2 levels (p less than 0.005). Abnormalities in collagen and ADP-induced platelet aggregation curves were also corrected, and ultrastructural abnormalities were not detected. Marked elevations in plasma thromboxane levels during ovine pregnancy-induced hypertension may have had an "exhaustive" effect on thrombocytes which was reversed by thromboxane synthetase inhibition.

Animals↗
PubMed1988

Erythrocyte morphologic features and serum chemistry studies in ovine pregnancy-induced hypertension treated with thromboxane synthetase inhibitors.

Erythrocyte morphologic characteristics and serum chemistry results were studied in 10 gravid ewes during experimental ovine pregnancy-induced hypertension and subsequent administration of the thromboxane synthetase inhibitors CGS13080 and CGS12970. During the hypertensive period mean arterial blood pressure, plasma thromboxane B2 levels, and serum chemistry results, and electrolyte levels were significantly altered. Parameters returned to baseline values or were improved after drug administration. Erythrocyte morphologic features did not change significantly with the onset of the syndrome. Echinocytosis was present during baseline measurement and persisted throughout hypertension. However, after thromboxane synthetase inhibition, percentages of discocytes increased (p less than or equal to 0.005) with the same frequency that echinocyte numbers decreased (p less than or equal to 0.05). Schistocytes were present throughout the study, and changes in their numbers were not detected. Serum phosphorus, blood urea nitrogen, and bilirubin levels and anion gap rose significantly during hypertension and returned to normal levels after drug treatment. We speculate that CGS13080 or CGS12970, by decreasing thromboxane levels and blood pressure, promoted the normalization of erythrocyte membranes.

Animals↗
PubMed1987

Endocardial fibroelastosis and tricuspid valve insufficiency in a calf.

A 5-month-old Holstein heifer had clinical signs of tricuspid valve insufficiency and histopathologic evidence of endocardial fibroelastosis. The calf had a 3-week history of weight loss, abdominal distention, dyspnea, and decreased appetite. Physical examination revealed signs of right-sided heart failure, and a systolic murmur (II/VI) was heard best over the right heart base. Results of cardiac catheterization and echocardiography indicated tricuspid valve insufficiency and right-sided heart failure. The calf was euthanatized after not responding to treatment with penicillin, furosemide, and removal of fluid from the thorax and abdomen. Necropsy findings included multifocal areas of thickening and opacification of the endocardium of the left and right ventricles. Excessive elastic fibers, consistent with fibroelastosis, were seen by use of special stains applied to sections of endocardium.

Animals↗
PubMed1987

Beneficial effects of U-63,557A, a thromboxane synthetase inhibitor, in an ovine model of pregnancy-induced hypertension.

Pregnancy-induced hypertension was induced in five ewes (gestational day 135; term 150 days) by 72 hours of food deprivation. Maternal arterial pressure, uterine blood flow, platelet function, renal function, and plasma levels of 6-ketoprostaglandin F1 alpha and thromboxane B2 were measured before and during hypertension and after three intravenous injections of U-63,557A; sodium 5-(3'-pyridinylmethyl) benzofuran-2-carboxylate, monohydrate (30 mg/kg every 8 hours). Blood pressure increased (p less than 0.03), and returned to normal after U-63,557A. Left uterine artery blood flow increased after U-63,557A (p less than 0.03). Creatinine clearance decreased during hypertension (p less than 0.03) and increased after U-63,557A. Urine protein increased during hypertension (p less than 0.03) and decreased after treatment. Platelet count dropped during hypertension (p less than 0.03) and was elevated after treatment. Collagen lag phase decreased during hypertension (p less than 0.03) and increased after treatment. After U-63,557A, 6-ketoprostaglandin F1 alpha levels were higher (p less than 0.04) than baseline or hypertensive values. Administration of a thromboxane synthetase inhibitor caused resolution of hemodynamic, renal, and coagulation dysfunctions that occurred in ovine pregnancy-induced hypertension.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Topographic localization of gastric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation.

The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3- concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis.

Animals↗
PubMed1987

A study of atherosclerotic lesion development in the injured pulmonary arteries of dogs with induced hyperlipemia.

Studies of experimental atherosclerosis in the dog demonstrate that many months at plasma cholesterol concentrations greater than 750 mg/dl are required to produce lipid containing atherosclerotic lesions. Since it has been recognized for many years that vascular injury in combination with hyperlipemia will result in rapid formation of atherosclerotic lesions, we attempted to combine vascular injury with hyperlipemia as a means of accelerating this process in the dog. Injury was produced in pulmonary arteries with experimental Dirofilaria immitis (DI or heartworm) infection. This filarial parasite produces characteristic lipid-free lesions containing smooth muscle cells and occasional monocytes and collagen. Plasma cholesterol was increased by feeding 10 dogs an essential fatty acid-deficient diet (EFAD) for 90 days. Five of the EFAD dogs were infected with 30 to 31 adult DI worms to produce pulmonary artery injury. The remaining 5 EFAD dogs were not subjected to any form of vascular injury. An additional 5 control dogs were not subjected to vascular injury nor to the EFAD diet. The arteries of dogs infected with DI developed myointimal proliferative lesions which contained smooth muscle cells and macrophages. In addition, the EFAD diet produced significant elevations in LDL but not VLDL plasma cholesterol in all 10 dogs fed the diet. However, the plasma cholesterol was less than 750 mg/dl in all EFAD-fed dogs. Although smooth muscle cells and macrophages in the pulmonary arteries of DI-infected dogs were focal points for lipid accumulation, cholesterol content of these injured arteries was not increased compared to noninjured EFAD dogs. The results suggest that even severe vascular injury does not reduce the threshold of 750 mg/dl required to produce significant lipid accumulation in canine arteries.

Animals↗
PubMed1986

Pregnancy-induced hypertension: development of a model in the pregnant sheep.

Selected hemodynamic, renal, and biochemical parameters were assessed in chronically instrumented third-trimester pregnant ewes and in the same ewes after induction of pregnancy toxemia. Ewes with induced pregnancy toxemia developed hypertension, proteinuria, ketonuria, decreased glomerular filtration rate, decreased cardiac output, and decreased left uterine artery blood flow. Histological and transmission electron microscopy revealed the development of renal morphologic changes consistent with those observed in human pregnancy-induced hypertension. These studies have elucidated that pregnancy-induced hypertension can be produced experimentally in the pregnant ewe. Furthermore, the pathophysiologic features of ovine pregnancy toxemia are similar to those of human preeclampsia, and therefore the sheep provides a suitable animal model to study the human condition, which still remains a major complication of pregnancy, jeopardizing both mother and fetus.

Animals↗
PubMed1986

Effect of lidocaine pretreatment on acute hemorrhagic shock in the anesthetized rat.

The hemodynamic and ultrastructural effects of lidocaine HCl pretreatment were assessed on anesthetized rats subjected to acute hemorrhagic shock. After 40 minutes of acute hemorrhagic shock (mean arterial pressure = 40 mmHg), significantly less fluid infusion was needed to return mean arterial pressure to 120 mmHg in lidocaine HCl treated animals as compared to the hemorrhagic shock-untreated group (p less than 0.05). Heart rate was significantly lower in lidocaine treated animals in the immediate post-shock period (p less than 0.05). Twenty minutes after resuscitation from shock, arterial pressures, and heart rate were not significantly different from baseline values in the lidocaine HCl group. However, in the hemorrhagic shock-untreated group all arterial pressures were still significantly lower than their baseline values (p less than 0.05). Ultrastructural myocardial ischemic changes appeared to be less severe in the lidocaine HCl treated animals. Lidocaine HCl pretreatment improved the response to hemorrhagic shock and reinfusion in this model of hemorrhagic shock.

Animals↗
PubMed1985

Smooth muscle proliferation in chronically injured canine pulmonary arteries is reduced by a potent platelet aggregation inhibitor U-53,059.

Dirofilaria immitis (DI) infection chronically injures canine pulmonary arteries. This injury produces endothelial cell loss, platelet/leukocyte adhesion, and smooth muscle proliferation. In the present study we assessed the effect of the cyclooxygenase inhibitor, U-53,059, on platelet function, platelet kinetics, coagulation, and smooth muscle proliferation in DI infected dogs. Platelet aggregation to the combination of arachidonic acid/ADP was significantly inhibited by U-53,059. Coagulation and hematologic parameters were not effected by either DI infection or U-53,059 treatment. Platelet survival and the number of platelet dense granules were reduced in DI infection. Quantification of the lesions demonstrated that U-53,059 reduced both severity and density compared to non-treated dogs. U-53,059 is a potent and effective inhibitor of platelet aggregation which modifies smooth muscle proliferation produced by chronic vascular injury.

Animals↗
PubMed1985

Ultrastructure of the stomach of the small short-tailed shrew, Blarina brevicauda c.

The normal gastric ultrastructure has been characterized for the small short-tailed shrew, Blarina brevicauda c., which is a primitive eutherian and one of the smallest living mammals with extraordinarily high metabolic rate. In general the cell types present and cytologic character of gastric mucosal, submucosal, and muscularis cells were similar to that reported for other more advanced small mammalian species. Chief cells, endocrine cells, and lamina proprial elements were morphologically identical to their counterpart in rats, ferrets and other small carnivores. Distinctive cytologic features in this species of shrew included the scanty monolayer or small number of mucous granules in the simple columnar surface epithelial cells of the mucosa, and the thin elongated shape of their microvilli. Dense bodies were absent in the parietal cell mitochondria of the shrew, though usually abundant in other mammalian parietal cells. Our data indicate few morphologic specializations in the shrew stomach which can be correlated with their high rate of food assimilation and metabolic demands, though future studies of mucosal biochemistry and lower gut morphology may reveal such adaptations.

Animals↗
PubMed1984

Blood pressures obtained by indirect measurement in conscious dogs.

Heart rate and arterial systolic, mean, and diastolic blood pressures were measured indirectly in apparently healthy dogs in clinical situations (examination rooms, cages, or runs) and in 3 groups of abnormal dogs. An electronic automatic sphygmomanometer measured and analyzed arterial pulses (oscillometric method). Apparently healthy dogs had a mean +/- SD heart rate of 134 +/- 32 beats/min and systolic, mean, and diastolic pressures of 144 +/- 27, 110 +/- 21, and 91 +/- 20 mm of Hg, respectively. The mean systolic pressure was significantly higher in hospitalized dogs than in nonhospitalized dogs. When compared with relaxed dogs, playful dogs had a higher mean heart rate. Apprehensive dogs had a higher mean diastolic pressure than did relaxed dogs. The mean heart rate and blood pressures of panting dogs were not significantly different from the mean values from relaxed dogs. Heavier (greater than 18 kg) and older (greater than 2 years) dogs had lower mean heart rates and higher pressures, compared with lighter (less than or equal to 18 kg) and younger (less than or equal to 2 years) dogs. Infection with Dirofilaria immitis had no effect on heart rate and blood pressures when compared with apparently healthy dogs. Dogs with renal failure had a significantly higher mean diastolic pressure and dogs with mitral regurgitation had a significantly lower mean diastolic pressure, compared with apparently healthy dogs.

Age Factors↗