Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine.

Gut epithelial apoptosis is involved in the pathophysiology of multiple diseases. This study characterized intestinal apoptosis in three mechanistically distinct injuries with different kinetics of cell death. FVB/N mice were subjected to gamma radiation, Pseudomonas aeruginosa pneumonia or injection of monoclonal anti-CD3 antibody and sacrificed 4, 12, or 24 hours post-injury (n=10/time point). Apoptosis was quantified in the jejunum by hematoxylin and eosin (H&E), active caspase-3, terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling (TUNEL), in situ oligoligation reaction (ISOL,) cytokeratin 18, and annexin V staining. Reproducible results were obtained only for H&E, active caspase-3, TUNEL and ISOL, which were quantified and compared against each other for each injury at each time point. Kinetics of injury were different with early apoptosis highest following radiation, late apoptosis highest following anti CD3, and more consistent levels following pneumonia. ISOL was the most consistent stain and was always statistically indistinguishable from at least 2 stains. In contrast, active caspase-3 demonstrated lower levels of apoptosis, while the TUNEL assay had higher levels of apoptosis in the most severely injured intestine regardless of mechanism of injury. H&E was a statistical outlier more commonly than any other stain. This suggests that regardless of mechanism or kinetics of injury, ISOL correlates to other quantification methods of detecting gut epithelial apoptosis more than any other method studied and compares favorably to other commonly accepted techniques of quantifying apoptosis in a large intestinal cross sectional by balancing sensitivity and specificity across a range of times and levels of death.

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience.

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.

Appetitive and consummatory sexual behaviors of female rats in bilevel chambers. I. A correlational and factor analysis and the effects of ovarian hormones.

This study investigated measures of sexual behavior displayed by female rats in bilevel chambers, the statistical relationships among the measures, and their dependency on hormone priming. Normative data from a standard 35-min test of sexual behavior were gathered from 82 fully primed sexually experienced Long-Evans females and subjected to multiple correlational and factor analyses. Several consummatory measures of copulation were related significantly, whereas appetitive level changing was statistically independent of consummatory measures. Factor analyses were conducted using orthogonal rotations of correlational matrices derived either from (a) measures of female behavior alone or (b) measures of female and male behavior together. The first analysis revealed five factors that accounted for 84% of the intersubject variance: Receptivity, Pacing, Appetitive Level Changing, Lordosis Reflex, and Solicitation. The second factor analysis with male data included revealed seven factors that accounted for 95% of the intersubject variance: Pacing, Copulatory Rate, Mount Count, Receptivity, Appetitive Level Changing, Solicitation, and Lordosis Reflex. Subsequently, subsets of these females were maintained on different steroid priming regimens (oil, low estrogen, high estrogen, high estrogen and progesterone) prior to a standard test of sexual behavior. Although the expression of all sexual behaviors required estrogen priming, appetitive level changing, solicitation, and pacing required progesterone for their full expression. Finally, appetitive level changing developed following hormone treatment alone, regardless of whether the females received access to sexually active males, inactive castrated males, or other females. Use of bilevel chambers allows complex patterns of sexual behavior to be observed in female rats and may thus facilitate the identification of neurochemical or endocrine mechanisms associated with different aspects of female sexual motivation and performance.

Unusual presentations of nonmycotic hepatic artery pseudoaneurysms after liver transplantation.

The clinical presentation and causes of hepatic artery pseudoaneurysm vary widely in the postoperative liver transplant recipient, although infection is the most common cause. Although uncommon, hepatic artery complications continue to be an important source of morbidity in liver transplant recipients. Thrombosis, stenosis, and pseudoaneurysm formation are the most common posttransplantation arterial complications. Pseudoaneurysms are most commonly mycotic in origin. Prompt recognition of hepatic artery pseudoaneurysms with aggressive intervention (both surgical and angiographic) may decrease the morbidity associated with this rare clinical entity. The records of 263 consecutive patients who underwent orthotopic liver transplantation between 1991 and 1996 were reviewed retrospectively and assessed for hepatic artery complications. Two patients (0.7%) developed hepatic artery pseudoaneurysm, neither associated with infection. Both patients required operative repair and are doing well without vascular complications at a mean follow-up of 22.5 months. The clinical presentation and causes of hepatic artery pseudoaneurysm vary widely in the postoperative liver transplant recipient. Prompt recognition of hepatic artery pseudoaneurysms with aggressive intervention (both surgical and angiographic) may decrease the morbidity associated with this rare clinical entity.

Bcl-2 inhibits ischemia-reperfusion-induced apoptosis in the intestinal epithelium of transgenic mice.

Little is known about the effects of ischemia-reperfusion on the inductive, commitment, or execution phases of apoptosis. We have created a genetically defined model to study the response of small intestinal epithelial cells to ischemia-reperfusion injury as a function of their proliferative status and differentiation. Occlusion of the superior mesenteric artery for 20 min in adult FVB/N or C57BL/6 mice results in the appearance of TUNEL-positive apoptotic cells in the jejunal epithelium within 4 h, with a maximum response occurring at 24 h. Stimulation of apoptosis is greater in postmitotic, differentiated epithelial cells located in the upper portions of villi compared with undifferentiated, proliferating cells in the crypts of Lieberkühn (7-fold vs. 2-fold relative to sham-operated controls). Comparisons of p53(+/+) and p53(-/-) mice established that the apoptosis is p53 independent. To further characterize this response, we generated FVB/N transgenic mice that express human Bcl-2 in epithelial cells distributed from the base of crypts to the tips of their associated villi. The fivefold elevation in steady-state Bcl-2 concentration is not accompanied by detectable changes in the levels or cellular distributions of the related anti-apoptotic regulator Bcl-xL or of the proapoptotic regulators Bax and Bak and does not produce detectable effects on basal proliferation, differentiation, or death programs. The apoptotic response to ischemia-reperfusion is reduced twofold in the crypts and villi of transgenic mice compared with their normal littermates. These results suggest that both undifferentiated and differentiated cells undergo a commitment phase that is sensitive to Bcl-2. Forced expression of Bcl-2 also suppressed the p53-dependent death that occurs in proliferating crypt epithelial cells following gamma-irradiation. Thus suppressibility by Bcl-2 operationally defines a common feature of the apoptosis induced in the crypt epithelium by these two stimuli.

Surgery of the small intestine.

This article reviews both clinical and scientific advances in surgery of the small intestine that have been reported in the last year. The management of both pediatric and adult intussusception is considered. Multiple studies on the evolving role of ileal pouch-anal anastomosis are assessed. The treatment and epidemiology of a wide variety of intestinal neoplasms are reviewed. Advances in small bowel transplantation are also reported. The cause of small bowel obstruction is considered as well as new strategies to prevent adhesion formation. Finally, a number of diverse topics relating to intestinal surgery, including new data on laparoscopic surgery, treatment of enterocutaneous fistulas, reconstruction after total gastrectomy, intestinal transit after ileocecal segment transposition, and ischemia/reperfusion and anastomotic healing, are reviewed.

Pregnancy block in house mice (Mus domesticus) as a function of t-complex genotype: examination of the mate choice and male infanticide hypotheses.

Pregnancy block, whereby recently mated female mice abort their pregnancies when exposed to novel (strange) males, was studied in house mice (Mus domesticus) differing in t-complex genotype; t-mutations are deleterious and +/t females avoid +/t males as mates. The results of Experiment 1, in which the genotype of the female, stud male, and strange male was systematically varied, showed that pregnancy block was most frequent when the strange male was +/+. Because this effect was not enhanced among +/t females when stud males were +/t, the results cannot clearly be explained by the hypothesis that pregnancy block is a manifestation of mate choice. Moreover, the "strange male" effect in Experiment 1 is unlikely to be a female response correlated with the risk of male infanticide, as +/+ and +/t males did not differ in their infanticidal tendencies (Experiments 2 & 3). Alternative hypotheses, including a modified version of the mate choice hypothesis, are discussed.

gamma-Ray-induced apoptosis in transgenic mice with proliferative abnormalities in their intestinal epithelium: re-entry of villus enterocytes into the cell cycle does not affect their radioresistance but enhances the radiosensitivity of the crypt by inducing p53.

The radiosensitivity of proliferating crypt epithelial cells makes the gut a major limiting factor in the use of radiotherapy for treatment of abdominal cancers. As post-mitotic epithelial cells migrate from mouse small intestinal crypts to the base of adjacent villi, they rapidly lose their ability to undergo apoptosis in response to ionizing irradiation (IR). To determine whether this radioresistance reflects withdrawal from the cell cycle, we used a lineage-specific promoter to direct expression of wild type Simian virus 40 T antigen (SV40 TAg(Wt)) to villus, but not crypt, enterocytes in FVB/N transgenic mice. SV40 TAg(Wt) induced, pRB-dependent, re-entry into the cell cycle is not associated with the acquisition of IR-stimulated apoptosis 4 h or 24 h after 6 Gy or 12 Gy of gamma-irradiation. Co-expression of SV40 TAg(Wt) and K-ras(val12) produces dysplasia in cycling villus enterocytes but no shift towards apoptotic responsiveness to IR. These findings suggest that the radioresistance of villus enterocytes is not simply due to their cell cycle arrest and may be a reflection of their microenvironment. Remarkably, reentry of villus enterocytes to the cell cycle increases the radiosensitivity of the crypt epithelium without changing Bcl-2, Bcl-xL, Bak, or Bax expression. This effect is only manifest after IR and, based upon results obtained with mutant SV40 TAgs, depends upon reaching a critical level of proliferation in villus enterocytes. Like the normal crypt response to IR, the villus-derived enhancement of IR-stimulated crypt apoptosis is associated with an induction of p53 and Raf-1, and is dependent upon p53. Unlike the normal crypt response to IR, the p53 induction involves cells distributed throughout the crypt and the apoptotic response is not confined to the lower half of the crypt. These results indicate that signals initiated by cycling enterocytes can be transmitted to the crypt epithelium to induce p53 and influence their IR-induced apoptosis. Understanding the underlying signaling pathways may provide clues about how to modify a normal crypt's radiosensitivity for therapeutic benefit.

Bi-transgenic mice reveal that K-rasVal12 augments a p53-independent apoptosis when small intestinal villus enterocytes reenter the cell cycle.

Studies in cell culture systems have indicated that oncogenic forms of Ras can affect apoptosis. Activating mutations of Ras occur in approximately 30% of all human tumors and 50% of colorectal carcinomas. Since these mutations appear at early or intermediate stages in multistep journeys to neoplasia, an effect on apoptosis may help determine whether initiated cells progress towards a more neoplastic state. We have tested the effects of K-rasVal12 on apoptosis in transgenic mice. A lineage-specific promoter was used to direct expression of human K-rasVal12, with or without wild-type (wt) or mutant SV-40 T antigens (TAg), in postmitotic villus enterocytes, the principal cell type of the small intestinal epithelium. Enterocytes can be induced to reenter the cell cycle by TAgWt. Reentry is dependent upon the ability of TAg to bind pRB and is associated with a p53-independent apoptosis. Analyses of K-rasVal12 x TAgWt bi-transgenic animals indicated that K-rasVal12 can enhance this apoptosis threefold but only in cycling cells; increased apoptosis does not occur when K-rasVal12 is expressed alone or with a TAg containing Glu107,108two head right arrow Lys107, 108 substitutions that block its ability to bind pRB. Analysis of bi-transgenic K-rasVal12 x TAgWt mice homozygous for wild-type or null p53 alleles established that the enhancement of apoptosis occurs through a p53-independent mechanism, is not attributable to augmented proliferation or to an increase in abortive cell cycle reentry (compared to TAgWt mice), and is not associated with detectable changes in the crypt-villus patterns of expression of apoptotic regulators (Bcl-2, Bcl-xL, Bak, and Bax) or mediators of epithelial cell-matrix interactions and survival (e.g., alpha5beta1 integrin and its ligand, fibronectin). Coexpression of K-rasVal12 and TAgWt produces dysplasia. The K-rasVal12-augmented apoptosis is unrelated to this dysplasia; enhanced apoptosis is also observed in cycling nondysplastic enterocytes that produce K-rasVal12 and a TAg with a COOH-terminal truncation. The dysplastic epithelium of K-rasVal12 x TAgWt mice does not develop neoplasms. Our results are consistent with this finding: (a) When expressed in initiated enterocytes with a proliferative abnormality, K-rasVal12 facilitates progression to a dysplastic phenotype; (b) by diminishing cell survival on the villus, the oncoprotein may impede further progression; and (c) additional mutations may be needed to suppress this proapoptotic response to K-rasVal12.

Use of normal and transgenic mice to examine the relationship between terminal differentiation of intestinal epithelial cells and accumulation of their cell cycle regulators.

A spatially well organized continuum of proliferation, differentiation, and death is displayed along crypt-villus units in the adult mouse small intestine. This continuum provides an opportunity to examine in vivo the mechanisms by which proliferative status changes as a function of cellular differentiation. Immunohistochemical studies of normal FVB/N mice revealed that as epithelial cells complete their terminal differentiation during a 48-72-h migration up villi, there is a marked and rapid fall in the levels of two important regulators of the G1/S transition, cyclin D1 and cyclin-dependent kinase (cdk) 2. However, cellular levels of their partners, cdk4 and cyclin E, remain unchanged as does the level of pRB. Adult FVB/N transgenic mice were studied that contained an intestinal fatty acid binding protein gene promoter (Fabpi) linked to wild type Simian virus 40 large T antigen (SV40 TAgWt) or a mutant TAg with Lys for Glu substitutions at residues 107 and 108 (SV40 TAgK107/8) that fails to bind pRB and related pocket proteins. Both transgenes are expressed only in villus enterocytes. SV40 TAgWt causes these terminally differentiated cells to re-enter the cycle. Re-entry is accompanied by a reduction in un/hypophosphorylated pRB, an induction of cyclin D1 and cdk2, but no change in cdk4, cyclin E, or E2F-1. In contrast, SV40 TAgK107/8 fails to induce re-entry and does not produce changes in un/hypophosphorylated pRB, cyclin D1, or cdk2 accumulation. These results suggest that un/hypophosphorylated pRB is an important mediator of the cell cycle arrest that normally occurs as enterocytes exit the crypt and complete their differentiation. Fabpi-directed expression of E2F-1 does not cause villus enterocytes to return to the cell cycle, alter their suppression of cyclin D1 or cdk2, or affect their state of differentiation, emphasizing the insensitivity of these cells to the effects of E2F-1. Analyses of p53(-/-) and p53(+/+) mice containing Fabpi-SV40 TAgWt and Fabpi-SV40 TAgK107/8 established that the proliferation induced by SV40 TAgWt does not require p53 and is associated with increased (p53-independent) apoptosis. The presence of cyclin E and cdk4 in differentiating villus enterocytes emphasizes that these cells retain part of their proliferative heritage expressed 24-72 h earlier in the crypt. The data suggest that down-regulation of cdk2 and/or cyclin D1 expression may be important for control of proliferative status and/or execution of terminal differentiation.

Effects of paced mating and intromissive stimulation on feminine sexual behavior and estrus termination in the cycling rat.

The effects of differential mating stimulation on sexual behavior and estrus length were examined in cycling rats that could or could not self-regulate, or pace, the timing of sexual contact. Female rats (Rattus norvegicus) received 30 paced, 30 nonpaced, or 15 nonpaced followed by 15 paced intromissions during mating tests. Decreases in sexual responsiveness were seen during the second half of testing; pacing was associated with greater inter-intromission intervals, decreased proceptivity, and increased rejection behavior at this time. Female rats pacing during the second test half behaved similarly, regardless of prior treatment, showing that the number rather than the timing of prior intromissions affected subsequent behavior. However, estrus length was decreased by prior paced mating. These data suggest that changes in sexual responsivity occur throughout estrus and that the nature of these changes is differentially dependent on the type of mating stimulation received.

Effects of paced and non-paced mating stimulation on plasma progesterone, 3 alpha-diol and corticosterone.

In the female rat, gonadal and adrenal progestins and androgens modulate sexual receptivity and in turn, their levels increase in response to mating stimulation. Paced mating, in which the female controls the timing of sexual contacts with the male, is particularly effective at eliciting acute increases in progesterone (P) and 5 alpha-Androstane-3 alpha, 17 beta-diol (3 alpha-Diol). Interestingly, restraint stress produces comparable increases in P and 3 alpha-Diol levels, as well as increases in corticosterone (CORT) levels. In this study, we explored the possibility that paced mating would be associated with increased CORT, in conjunction with mating-induced increases in P and 3 alpha-Diol. Ovariectomized rats primed with estradiol benzoate (10 micrograms in oil SC) and P (0.5 mg in oil s.c.) received a single ejaculatory series from males in paced or non-paced mating tests. Fifteen minutes post-mating rats were exposed to CO2 and rapidly decapitated for the collection of trunk blood and determination of P, 3 alpha-Diol and CORT via radioimmunoassay. As expected, P and 3 alpha-Diol concentrations were significantly elevated in serum obtained from animals allowed to pace their sexual contacts with males compared to those which did not pace their contacts. Importantly, although all mated animals had CORT levels between 10-20 micrograms/dl, there were no differences between paced and non-paced conditions. This suggests that the acute rises in P and 3 alpha-Diol in response to paced mating are not due to paced mating being more stressful than non-paced mating.

Infusions of lidocaine into the amygdala, but not the preoptic area, block pseudopregnancy in the rat.

In the rat, vaginocervical stimulation (VCS) received during mating is required for the subsequent expression of 10-12 days of twice-daily prolactin surges that are necessary for pregnancy or pseudopregnancy (PSP). This temporal separation of sensory stimulus and neuroendocrine response suggests that a mnemonic of the vaginocervical stimulation is created in the brain that triggers and sustains the daily prolactin surges. We investigated the possible involvement of the medial preoptic area (mPOA) and the medial amygdala (mAMYG) as potential neural sites involved in the processing of this neuroendocrine arc. Cycling female rats were bilaterally implanted with intracerebral cannulae in either the mPOA or mAMYG. On proestrus, females were manually palpated to confirm sexual receptivity and then received bilateral infusions of either the local anesthetic lidocaine, the Ca(++) channel blocker, verapamil, or phosphate-buffered saline (PBS) into either brain site before or both before and after receipt of 15 intromissions from an experienced male. Unmated control females received comparable infusions of lidocaine or verapamil, and were placed in the empty test arena for 10 min. Infusions consisted of either a single bilateral infusion 15 min before mating (Expt. 1), bilateral infusions both 15 min before and after mating (Expt. 2) or eight bilateral infusions separated by 30 min intervals spanning a period beginning 45 min before and ending 2 h 45 min after mating (Expt. 3). None of the lidocaine infusions into the mPOA prevented the establishment of PSP, and neither verapamil infusions into the mAMYG nor the shorter-term neural block (i.e. single or double lidocaine infusions) of the mAMYG prevented mating-induced PSP. However, the longer-term neural block (i.e. multiple lidocaine infusions) of the mAMYG significantly reduced the incidence of PSP. These data support previous findings that the mAMYG receives sensory input from VCS, and suggest that the mAMYG is a site at which a mnemonic of VCS is established.

Influence of paced mating and number of intromissions on fertility in the laboratory rat.

The effects of differential mating stimulation on fertility in rats were examined by mating pro-oestrous females for one ejaculatory series in tests in which they could or could not self-regulate, or pace, the timing of intromissions received by males. Females were autopsied on days 7, 14 or 21 after mating, or on the expected day of birth to confirm pregnancy, and the number of implantation sites or of viable fetuses or pups determined. Because of substantial behavioural variability within an ejaculatory series, data from paced and nonpaced females were divided according to whether they received a low (< or = 8) or high (> or = 9) number of intromissions. The incidence of pregnancy was significantly reduced among paced females receiving few intromissions relative to that of any other group. Histological examination of ovaries from females autopsied on day 7 after mating suggested that the reduced pregnancy rate among this paced, low intromission group resulted from a failure of activation of the corpora lutea, a possible consequence of the low number of intromissions received by these females. However, in paced, low intromission females that became pregnant, litter size was significantly greater than in nonpaced, low intromission females. These results suggest a compensatory effect of the temporal patterning of intromissive stimulation on fertility. This effect is not a consequence of differential mortality after implantation since there was no difference in litter size among females autopsied at any of the four times. The differences between paced and nonpaced females may be attributable to preimplantation effects such as differential release of ova or sperm transport.

Expression of wild-type and mutant simian virus 40 large tumor antigens in villus-associated enterocytes of transgenic mice.

The four principal gut epithelial cell lineages undergo continuous and rapid renewal during a geographically well-organized migration along the crypt-to-villus axis. The molecules that regulate their proliferation and differentiation programs are largely unknown. The large tumor antigen (TAg) of wild-type (wt) simian virus 40 (SV40) and its mutant derivatives represent tools for describing the contributions of regulators of the cell cycle to the proliferative state of each lineage. Expression of SV40 TAgwt in postmitotic, villus-associated enterocytes of transgenic mice causes them to reenter the cell cycle without an apparent effect on their state of differentiation. When human KRAS with a Val-12 substitution ([Val12]KRAS) is coexpressed with SV40 TAgwt in villus enterocytes of bitransgenic animals, the two oncoproteins cooperate to produce dedifferentiation (dysplasia). SV40 mutant d11137 expresses a TAg that is unable to complex with p53 but retains N-terminal transforming functions, including the ability to complex pRB, p107, and p300. When SV40 TAgd11137 is expressed in villus enterocytes, they reenter into the cell cycle. However, coexpression of SV40 TAgd11137 and [Val12]KRAS does not produce dysplastic changes. Thus, the N-terminal 121 residues of TAg are sufficient to perturb the proliferative state of the enterocyte but not to produce detectable changes in the state of differentiation when coexpressed with [Val12]KRAS.

Effects of pre- and postpubertal social experience on sexual and social behavior in male and female brown lemmings (Lemmus sibiricus).

The effects of prepubertal social contact and postpubertal mating experience on sexual behavior were examined in male and female brown lemmings (Lemmus sibiricus). Subjects of both sexes were either isolated at weaning (18 days) or then housed with siblings for another 10 days before being isolated. Before testing for sexual behavior at the age of 75 days, half of each group of males received a series of exposures to estrous females and half of each group of females was housed with a stud male. The results of mating tests indicated that whereas prior sexual experience facilitated subsequent copulatory behavior in both sexes, prepubertal interactions subsequently facilitated contact social and sexual behavior in males but did not increase the behavioral scores of females, which engaged in high levels of sexual behavior regardless of prepubertal experience. The effect of prior copulatory activity on male sexual performance could not be attributed to increasing age (i.e., maturational processes) because the behavior of males tested once but at different ages did not differ appreciably. Prepubertal social interaction appeared to predispose males to benefit from sexual experience later in life.

Social olfaction in male brown lemmings (Lemmus sibiricus = trimucronatus) and collared lemmings (Dicrostonyx groenlandicus): II. Discrimination of mated and unmated females.

When tested in a Y-maze olfactometer, male brown and collared lemmings (Lemmus sibiricus = trimucronatus and Dicrostonyx groenlandicus) preferred the odor of unmated receptive females to the odor of females with which they had just copulated. Similarly, sexually satiated males preferred the odor of an unmated receptive female to that of a strange female that had recently copulated with another male. Sexually experienced males without recent copulatory experience also demonstrated this preference, but sexually naive males did not. Sexually satiated collared lemmings preferred the odor of bedding from a novel estrous female to bedding from the female with which they had just copulated even when the bedding was collected before mating occurred. These results suggest that discrimination between prior mates and unmated females may be based on individual recognition as well as recognition of subclasses of females (i.e., mated vs. unmated, familiar vs. unfamiliar).

Effects of olfactory cues on sexual behavior in the brown lemming, Lemmus trimucronatus.

Three groups of female lemmings were tested to determine the effects of odor familiarity on measures of reproductive behavior. A familiar odor (FO) group was exposed to the bedding of a particular male for 1 wk, then tested with that male. A second female group (unfamiliar odor; UO) was exposed to the bedding of a male for 1 wk, then tested with a different male. A third group (control; CO) was not exposed to male bedding prior to being tested with a male. The FO females engaged in higher frequencies of contact social behaviors than did UO and CO females. Males with FO females ejaculated more frequently than did the males with UO and CO females. Latencies to first display of sexual behaviors (female: lordosis; male: mount, thrust, and ejaculation) were lower for FO pairs. These results suggest that previous exposure of females to the odor of a given male facilitates sexual behaviors when such females are later paired with that male.