The normal and abnormal owl monkey (Aotus sp.) heart: looking at cardiomyopathy changes with echocardiography and electrocardiography

Background Cardiovascular disease, especially cardiomyopathy, was the major cause of death among owl monkeys (Aotus sp.) at a major colony and threatened colony sustainability. For this study, echocardiography (echo) and electrocardiography (ECG) normal values were established, and cardiomyopathy animals identified. Methods Forty‐eight owl monkeys were studied, 30 older than 10 years of age (‘aged’) and 8 of age 5 years (‘young’). Eight aged owl monkeys had cardiomyopathy. Results and Conclusions Aged Aotus had increased left ventricular posterior wall thickness over young animals. Left ventricular diameter and ejection fraction appeared to be the best identifying measurements for cardiomyopathy. There were no differences in the ECG.     

Dilative cardiomyopathy leading to congestive heart failure in a male squirrel monkey (Saimiri sciureus)

A 17-year-old, 1-kg, colony-housed, male squirrel monkey (Samiri sciureus) developed clinical signs of congestive heart failure. The monkey presented with lethargy, increased heart and respiratory rates, and mild abdominal distention. The clinical history, laboratory analysis, and radiographic findings were consistent with heart failure due to dilative cardiomyopathy. Gross and microscopic examination of the heart confirmed a dilative cardiomyopathy. This is the first report describing congestive heart failure caused by dilative cardiomyopathy in a squirrel monkey. Spontaneous dilative cardiomyopathy may be infrequently observed in the squirrel monkeys because they are not routinely housed in the research environment during their advancing years.     

Developmental changes in ECG associated with heart rate are similar in squirrel monkey and human infants.

Interest in refining noninvasive methods of diagnosis and further characterization of squirrel monkeys (Saimiri sp.) as a model for pediatric cardiology studies led to this investigation of electrocardiogram (ECG) changes associated with changes in age and position. During a single delivery season, ECGs were performed at 1 day, 1 month, and 1 year of age. For each age group, ECGs were recorded with animals in dorsal, ventral, and right lateral recumbency. The 1-day-old group had the lowest heart rates (271 +/- 10, right lateral recumbency, mean +/- SEM) relative to the other age groups. One-year-old monkeys had heart rates of 333 +/- 18. One-month-old infants had rates significantly higher than the other two age groups (366 +/- 4). The QRS frontal-plane axis showed an age-related leftward change from 1 day (151 +/- 28 degrees) to 1 year of age (121 +/- 44 degrees) while the P-wave frontal plane axis remained nearly constant over a narrow range at all ages. The pattern of heart rate changes with age were similar to those in humans, although the ranges of absolute heart rates were markedly different. These data suggest that factors that influence maturational changes in heart rate, conduction time (as reflected by ECG intervals) and cardiac chamber size and position (inferred from axis and voltage) are similar among primates of widely variant body sizes.     

Phenotypic and Functional Characterization of Lymphocytes from Different Age Groups of Bolivian Squirrel Monkeys (Saimiri boliviensis boliviensis)

Due to many physiological and genetic characteristic similarities to humans, squirrel monkeys provide an ideal animal model specifically for studying malaria, and transmissible spongiform encephalopathies (Creutzfeldt-Jacob disease). While squirrel monkeys three years and older are generally considered adult subjects suitable for use in medical research studies, little is known about the functional properties of lymphocytes in relation to the age of these animals, which could significantly impact the quality and quantity of innate and adaptive immune responses. In this study, we investigated differences in the phenotype and function of lymphocytes subsets of young (3–4 years), adult (8–10 years) and aged (16–19 years) squirrel monkeys. In general, animals in all three age groups exhibited comparable numbers of different lymphocyte subsets except for CD20+ B cells that were significantly lower in aged relative to young animals and T cells subsets expressing both CD4 and CD8 (double positive) were significantly higher in aged relative to young animals. With increasing age, phenotypic differences in central and effector memory T cells subsets were observed, that were more pronounced for the CD8+ T cells. Despite equal proportions of CD3+ T cells among the three age groups, responses of peripheral blood mononuclear cells to T cell mitogens PHA and Con A showed lower IFN-γ producing cells in the aged group than that in the young group. Furthermore, aged animals showed significantly higher plasma levels of inflammatory cytokines IL-6, IFN-γ, TNF-α, IL-10 and IL-12. These findings suggest that while the squirrel monkeys in general share phenotypic and functional similarities of lymphocyte subsets with humans in relation to age, specific differences exist in immune function of lymphocytes between young and old animals that could potentially impact experimental outcomes for which the measurement of immunologic endpoints are critical.     

Age-related hormonal differences in cycling squirrel monkeys (Saimiri boliviensis boliviensis)

This study was planned to evaluate the poor reproductive performance of aged squirrel monkeys in a self-sustaining breeding colony. Two groups of monkeys aged 6–8 years (Group 1), and >12 years (Group 2) were evaluated. During the midbreeding season, daily blood samples were obtained for a period of 35 days from 10 animals in each group. Blood samples were assayed for serum estradiol (E), progesterone (P), and bioassayable luteinizing hormone (bio-LH) concentrations and the data were analyzed by ANOVA (analysis of variance). Bio-LH surges were less frequent in the aged breeders (Group 2). Total P output during periovulatory period (day ?;3 to day + 3) and the total P output during the luteal phases of the estrus cycles were significantly lower in aged squirrel monkeys (Group 2, P < 0.003). Although E peaks occurred less frequently in Group 2, they had higher concentrations as compared to Group 1 (P < 0.003). Cumulative periovulatory and luteal phase E levels did not differ between the two groups. The reduction in P output in aged squirrel monkeys may interfere with proper implantation, thus contributing to the lower pregnancy rate observed in this age group. The decreased frequency of bio-LH surges indicated less frequent ovulations in the aged animals which may further impair reproduction with aging. © 1994 Wiley-Liss, Inc.     

Experimental American leishmaniasis and Chagas'' disease in the Brazilian squirrel monkey: cross immunity and electrocardiographic studies of monkeys infected with Leishmania braziliensis and Trypanosoma cruzi

, and 1988. Experimental American leishmaniasis and Chagas' disease in the Brazilian squirrel monkey: cross immunity and electrocardiographic studies of monkeys infected with Leishmania braziliensis and Trypanosoma cruzi. International Journal for Parasitology 18: 1053–1059. Adult, laboratory-bred squirrel monkeys (Saimiri sciureus) previously infected with either Leishmania braziliensis braziliensis or L. b. panamensis were challenge infected with blood-form trypomastigotes of Trypanosoma cruzi (Brazil strain). Monkeys previously infected with T. cruzi were challenged with stationary phase promastigote forms of L. b. braziliensis. Monkeys were examined during the course of challenge for evidence of infection, electrocardiographic alterations and parasite-specific antibody responses. T. cruzi epimastigotes were cultured from the blood of monkeys up to 3 months after challenge with this parasite. Unulcerated cutaneous lesions appeared and persisted in monkeys challenged with L. b. braziliensis. The formation of satellite lesions was observed in one monkey. Increased QRS intervals were not observed in T. cruzi challenged monkeys without prior cardiac irregularities and QRS left axis shifts were observed in only two of these monkeys. Elevated titers of parasite binding IgM and IgG specific for both T. cruzi and L. braziliensis were observed in all monkeys following challenge. These results indicate that prior infection with T. cruzi or L. braziliensis does not protect against heterologous challenge infection with these organisms. However, prior infection with Leishmania parasites may provide some protection against chagasic cardiopathies.     

Comparative dipolar electrocardiotopographic study of ventricular activation in Macaca mulatta monkeys and man

Electrocardiographic correlates of ventricular activation sequence were studied in 22 Macaca mulatta monkeys, aged 1-18 years, and 145 human subjects, aged 11-72 years, using the corrected orthogonal lead system of McFee-Parungao and the dipolar electrocardiotopographic (DECARTO) data presentation, where the time series of instantaneous spatial vectors are converted into time series of areas of activation on a spherical image surface enveloping the heart. Macaques had shorter ventricular activation time (61+/-11 vs. 97+/-11 ms) that could not be explained exclusively by their higher heart rate. Their DECARTO image of the resultant activation front occurred 10 ms after QRS onset (septal activation) identically with humans, but it attained a more anteriorly oriented maximum earlier than in humans (20 vs. 40 ms). The time course of the extent of the resultant activation front in old macaques (15-18 years) resembled to that observed in humans. On the average, female macaques had smaller DECARTO images of activation fronts throughout the QRS complex than males. This finding is in agreement with the known smaller QRS amplitudes in women than in men.     

Squirrel monkey dominance and social behavior as related to group size and group structure

Adult male and female squirrel monkeys were tested in nonsocial adaptation and pairwise and triad social situations differing in sex composition. Social behaviors, nonsocial behaviors, and dominance hierarchies were observed during social testing. Dominance hierarchies were similar in groups differing in size and social structure. Nonsocial behaviors decreased in females and submissive animals paired with males or dominant monkeys. Aggressiveness between females decreased and the beginnings of coalitions between females were observed in the presence of a male. The social behavior patterns, but not dominance hierarchies, are consistent with behaviors observed in larger groups of squirrel monkeys.     

Cardiomyopathy in captive owl monkeys (Aotus nancymae)

Dilated cardiomyopathy (DCM) was identified histopathologically in a colony of owl monkeys (Aotus nancymae) over a 15-year period. We characterized the incidence of cardiac disease echocardiographically in the colony over a 14-month period. Of 77 monkeys, 21 had systolic myocardial failure, and postmortem examination confirmed the antemortem diagnosis of DCM in eight animals. Monkeys with a questionable diagnosis at the first examination demonstrated progression of disease with time. Left ventricular end-systolic cross-sectional area and left ventricular fractional area change were the indices that most reliably discriminated between normal and diseased animals. Serum cardiac troponin I concentrations were below detectable limits in normal and diseased monkeys. The apparent high prevalence of disease in this colony precluded establishment of reference intervals for Aotus nancymae. Our study provides the first comprehensive echocardiographic evaluation of owl monkeys with cardiomyopathy.     

Electrocardiographic studies in the Japanese monkey (Macaca fuscata) with special reference to the effect of anesthesia with barbiturates

The electrocardiograms of 157 healthy Japanese monkeys (Macaca fuscata), covering a wide range of ages in both sexes, were recorded under light pentobarbital (Nembutal) anesthesia. Although results were generally similar to those reported for other macaque species, some quantitative differences were observed.The heart rate was about 160 per minute in all monkeys examined; the P-Q interval was 0.11±0.06 sec.; the duration of QRS was 0.04±0.01 sec.; the Q-T interval was 0.24±0.06 sec. The mean axis of QRS was +59° and the pattern of the QRS complex was qR type in most cases.The comparison with the human electrocardiogram shows that the heart rate ofM. fuscata is about twice that of man, while the P-Q, QRS, and Q-T intervals were about one-half of those found in human subjects. In the monkey, however, the P wave was sharp and the T wave flat.In order to estimate the effect of anesthesia on the electrocardiogram, the records of several monkeys before, during, and after intravenous administration of barbiturates were compared. Although some animals showed extrasystoles after barbiturate was administered, generally no essential changes were noted in the records, except for the retardation of the rate and proportional prolongation of intervals.This work was presented at the 10th Annual Meeting of the Primate Research Association held in Inuyama, March 13, 1966.     

Is the endogenous antipyretic neuropeptide alpha-MSH responsible for reduced fever in aged rabbits?

The reduced febrile response in aged man has been noted since the beginning of clinical thermometry. Our previous research on aged rabbits and squirrel monkeys disclosed a similar reduced fever, presumably due to a decrease in central receptors for endogenous pyrogen. However, because central alpha-melanocyte stimulating hormone (MSH) appears to have a potent role in physiological control of fever, it may be that increased release of the peptide is responsible for the reduced febrile response in aged animals. To test this idea, antiserum specific to MSH was administered intracerebroventricularly to rabbits of known age. The antiserum given according to three schedules of treatment augmented fever caused by IV injections of interleukin-1 (IL-1) in young (less than 2 years) male and female rabbits. Aged female rabbits (3-5+ years) and females aged 2-3 years showed significant augmentation of fever only after pretreatment plus acute injection of antiserum. A single ICV injection of MSH (200 ng) reduced fever in all groups with the greatest antipyretic effect in the aged females. The results indicate that while aged rabbits have an increased antipyretic response to central MSH, binding of the endogenous peptide does not result in marked increases in fever in these animals. Thus, whereas a change in central MSH sensitivity may contribute to reduced fever in aged homeotherms, a reduction in central pyrogen receptors appears to be the most parsimonious explanation.     

Laterality in spontaneous motor activity of chimpanzees and squirrel monkeys

Varieties of nonmanipulative motor responses were observed in chimpanzees and squirrel monkeys. Chimpanzees displayed a right hand preference for touching their inanimate environments but used their right and left hands equally for touching their faces and their bodies. The latter result was not consistent with previous reports of a left hand preference for face touching in apes. The right hand preference for environmental touching was stronger in male than in female chimpanzees. Squirrel monkeys had a right preference for combined hand and foot responses directed to their bodies, but expressed no handedness for environmentally directed touching. These limb preferences in chimpanzees and squirrel monkeys indicate that neither precise, complex manipulation nor postural instability are necessary conditions for population level hand preferences. Factor analysis of the chimpanzee manual responses showed distinct self and environmentally directed factors. Analysis of the squirrel monkey data also showed self and environmental factors, except that body scratching had a negative loading on the environmental factor. This latter result suggests that self-scratching by squirrel monkeys is a displacement activity that suppresses manual exploration of the environment. © 1992 Wiley-Liss, Inc.     

Age-related diffuse chronic telogen effluvium- type alopecia in female squirrel monkeys (Saimiri boliviensis boliviensis)

We investigated the diffuse alopecia affecting some female squirrel monkeys (Saimiri boliviensis boliviensis) housed in a breeding facility. We randomly selected 100 female and 10 male animals and performed a complete physical exam and a hair assessment on all animals; blood tests, trichograms, hair density; and skin biopsies in representative cases; and a dominance behavioral assessment of 50 animals. Hair coat was normal in 35 female monkeys and all 10 male animals. Of the 65 females with diffuse alopecia, 17 had mild, 22 moderate, and 26 severe hair loss. The alopecia group had a mean age of 9.6 +/- 0.6 years, whereas that of the normal group was 4.7 +/- 0.6 years (P < 0.05). The parity in the alopecia group was 4.2 +/- 0.6 but 2.0 +/- 0.6 (P < 0.05) in the normal group. There were no statistically significant differences in body weight, hemoglobin, blood urea nitrogen, serum glucose, liver aspartate aminotransaminase, or free thyroxine. The trichogram demonstrated 20.8% +/- 1.6% (mean +/- standard error) of telogen hairs in the alopecia group compared with 9.5% +/- 2.8% of the control group (P < 0.05). The hair density in the alopecia group was 52.8 +/- 4.1/cm2 and 79.6 +/- 14.3/cm2 in the control group. Skin biopsies in affected monkeys demonstrated increased telogen follicles, with no fibrosis or inflammation. There were no statistically significant differences in the dominance behavioral analysis. The findings are consistent with chronic telogen effluvium (CTE). A number of organic, behavioral, and dominance-related stress causes of CTE were excluded. CTE appears to be predominantly age-related in this population. CTE in female squirrel monkeys may serve as an animal model for human diffuse alopecia.     

Intracardiac thrombosis and aortic dissecting aneurysms in mustached tamarins (Saguinus mystax) with cardiomyopathy

Spontaneous intracardiac thrombosis is rarely reported in animals, particularly nonhuman primates. The finding of 2 cases of intracardiac thrombi in mustached tamarins (Saguinus mystax) that died as a consequence of congestive heart failure prompted us to do a retrospective study to determine the frequency of this condition. Clinical records, necropsy reports, and tissues from 60 mustached tamarins that died or were euthanized between 1996 and 2009 were reviewed. Of the 60 monkeys whose cases were reviewed, 10 (16.6%) had intracardiac thrombi, and 4 (6.6%) had dissecting aortic aneurysms. Of the 10 animals with intracardiac thrombosis, 3 had left ventricular involvement alone; 4 monkeys had thrombi only in the right ventricle, and the remaining 3 animals exhibited thrombi in both ventricles. Myocardial fibrosis and chronic renal disease were common findings in affected animals. The causes of the intracardiac thrombosis in the tamarins in the present study are not known, but the clinical signs and gross and microscopic lesions suggest that congestive heart failure secondary to cardiomyopathy is the primary contributor. In addition, the cause of the aortic dissecting aneurysms in the tamarins in this study is not known. Further studies are required to determine whether factors including aortic curvature, genetic background, or hypertension-alone or in combination-play a role. To our knowledge, the current retrospective study is the first report of intracardiac thrombosis and aortic aneurysms in mustached tamarins.     

Biologic data of Macaca mulatta, Macaca fascicularis, and Saimiri sciureus used for research at the Fiocruz primate center

Physiological parameters of laboratory animals used for biomedical research is crucial for following several experimental procedures. With the intent to establish baseline biologic parameters for non-human primates held in closed colonies, hematological and morphometric data of captive monkeys were determined. Data of clinically healthy rhesus macaques (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis), and squirrel monkeys (Saimiri sciureus) were collected over a period of five years. Animals were separated according to sex and divided into five age groups. Hematological data were compared with those in the literature by Student's t test. Discrepancies with significance levels of 0.1, 1 or 5% were found in the hematological studies. Growth curves showed that the sexual dimorphism of rhesus monkeys appeared at an age of four years. In earlier ages, the differences between sexes could not be distinguished (p < 0.05). Sexual dimorphism in both squirrel monkeys and cynomolgus monkeys occurred at an age of about 32 months. Data presented in this paper could be useful for comparative studies using primates under similar conditions.     

Seasonal changes of serum concentrations of estradiol and progesterone in Bolivian squirrel monkeys (Saimiri sciureus)

Serial measurements of estradiol (E2) and progesterone (P) were used to describe the ovarian cycle of the Bolivian squirrel monkey. Group-caged, sexually mature female squirrel monkeys, housed with males, were sampled daily between 0900 and 1100 hr. Sampling was carried out during the breeding and nonbreeding seasons, for periods of 19–20 days from September 1981 to May 1982. Seasonal differences in serum concentrations of E2 and P were found with low levels of E2 and P and an absence of preovulatory surges of E2 during the nonbreeding season. This pattern was also observed in some animals during the breeding season. An abrupt increase in serum P concentrations in December appeared to signal the onset of cycling. Cycling animals had well-defined peaks of E2 (450–9,500 pg/ml) followed by increasing levels of P, which were >200 ng/ml in some animals. After the breeding season, E2 and P levels returned to their initially low levels. Levels of both steroids in cycling animals were higher than those reported for other primates and for previous measurements made in squirrel monkeys. Cycle length based on time interval between consecutive E2 peaks varied from 6–12 days.     

In vitro regulation of cholesterol metabolism by low density lipoproteins in skin fibroblasts from hypo-and hyperresponding squirrel monkeys.

When squirrel monkeys (Saimiri sciureus) are fed diets containing cholesterol, some individuals (hyperresponders) become hypercholesterolemic, while others (hyporesponders) are able to maintain nearly normal plasma cholesterol concentrations. Skin fibroblasts were grown from three hyperresponder and threehyporesponder squirrel monkeys, previously characterized on the basis of their plasma cholesterol response to two cholesterol-containing diets and the pheno-type of their parents. The rates of cholesterol synthesis and esterification were determined in the cultured fibroblasts incubated with low density lipoproteins isolated from normocholesterolemic squirrel monkeys or hypercholesterolemic rhesus monkeys. Both lipoprotein preparations influenced the metabolic parameters measured in a similar manner in cells from both hypo- and hyperresponder animals. Exposure of skin fibroblasts to low density lipoproteins resultd in a stimulation of cholesterol esterification and a suppression of cholesterol synthesis in cells from both hypo- and hyperresponder animals. When incubated with increasing concentrations of low density lipoprotein cholesterol, up to 50 microgram/ml, fibroblasts from both hypo-and hyperresponding animals responded with a similar maximum percentage suppression of sterol synthesis. Thus, hyperresponsiveness to dietary cholesterol in squirrel monkeys, although a heritable characteristic, is not associated with an inability of low density lipoprotein to suppress cholesterol synthesis or stimulate cholesterol esterification as occurs in familial hypercholesterolemia in man.     

Suspected ascorbic acid deficiency in a colony of squirrel monkeys (Saimiri sciureus).

Subperiosteal cranial hematomas were observed in five female squirrel monkeys. The absence of trauma in the clinical history, the characteristic clinical changes, and the pathological lesions suggested that the animals were scorbutic. Analysis of feed which was soaked in water, or left on the ground for varying time periods at different temperatures, indicated that there was loss of ascorbic acid. During the manufacture of monkey feed, ascorbic acid is dusted on as a final process. The practice of soaking feed resulted in the "washing off" or the destruction of ascorbic acid. This disease outbreak emphasized the important of management practices in a primate colony.     

Clinical pathology data from cynomolgus monkeys from China in which diarrhea was observed during quarantine.

Shin Nippon Biomedical Laboratories, Ltd. (SNBL) imported and quarantined 3,148 cynomolgus monkeys (aged 2.5 to 6.5 years) from China in 2002. The hematology and blood biochemistry data obtained from these monkeys on Day 32 of quarantine were analyzed separately by sex [2,890 animals in which no abnormalities were observed during the 35-day quarantine period (normal group), and 258 animals which exhibited diarrhea 1 to 12 times (diarrhea group)]. The values obtained for all parameters were within the normal range (mean +/- SD), and no significant abnormalities were noted in either sex. The clinical pathology data from 11 animals (6 males and 5 females) exhibiting diarrhea repeatedly (10 to 12 times) were statistically analyzed, and significant differences were noted in PLT and ALP in both sexes. The PLT values of these animals were within the normal group mean +/- 2 SD, and were considered within the normal range. A significant difference was noted in some individual ALP values (males: Nos. 2 and 3, females: Nos. 1, 3, and 4). The clinical pathology data obtained from the normal group in this study basically correspond to the widely reported results already obtained from healthy cynomolgus monkeys, from which it can be concluded that the cynomolgus monkeys from China were generally healthy and presenting no particular abnormality. The clinical pathology data from the normal group will serve as valuable baseline data for experimenters using cynomolgus monkeys.     

Which senses play a role in nonhuman primate food selection? A comparison between squirrel monkeys and spider monkeys

In order to optimize foraging efficiency and avoid toxicosis, animals must be able to detect, discriminate, and learn about the predictive signals of potential food. Primates are typically regarded as animals that rely mainly on their highly developed visual systems, and little is known about the role that the other senses may play in food selection. It was therefore the aim of the present study to assess which senses are involved in the evaluation of food by two species of New World primates: the squirrel monkey and the spider monkey. To this end, six animals per species were repeatedly presented with both familiar and novel food items, and their behavior was videotaped and analyzed. To obtain a further indication of the relative importance of visual and chemosensory cues, the animals were also presented with familiar food items that were experimentally modified in color, odor, or both color and odor. The results demonstrate that squirrel monkeys and spider monkeys use olfactory, gustatory, and tactile cues in addition to visual information to evaluate novel food, whereas they mainly inspect familiar food items visually prior to consumption. Our findings also show that in both species the use of nonvisual cues decreased rapidly with repeated presentations of novel food, suggesting a fast multimodal learning process. Further, the two species clearly differ in their relative use of nonvisual cues when evaluating novel or modified food, with spider monkeys relying more on olfactory cues than squirrel monkeys, and squirrel monkeys relying more on tactile cues compared to spider monkeys.