Tibetans exhibit lower hemoglobin concentration and decreased heart response to hypoxia during poikilocapnia at intermediate altitude relative to Han Chinese.

Background: High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia. Methodology: We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300 m (∼4327 ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ V˙I/ΔPetCO2 and ΔHR/ΔPetCO2, respectively). Results: Male Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01). Conclusion: These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link.

Intermittent hypoxia, a feature of obstructive sleep apnoea, potentiates ventilatory hypoxic responses, alters heart rate variability and produces hypertension, partially owing to an enhanced carotid body responsiveness to hypoxia. Since oxidative stress is a potential mediator of both chemosensory and cardiorespiratory alterations, we hypothesised that an antioxidant treatment may prevent these alterations. Accordingly, we studied the effects of ascorbic acid (1.25 g.L(-1) drinking water) on plasma lipid peroxidation, nitrotyrosine and inducible nitric oxide synthase (iNOS) immunoreactivity in the carotid body, ventilatory and carotid chemosensory responses to acute hypoxia, heart rate variability and arterial blood pressure in male Sprague-Dawley rats exposed to 5% O(2); 12 episodes.h(-1); 8 h.day(-1) or sham condition for 21 days. Intermittent hypoxia increased plasma lipid peroxidation, nitrotyrosine and iNOS expression in the carotid body, enhanced carotid chemosensory and ventilatory hypoxic responses, modified heart rate variability and produced hypertension. Ascorbic acid prevented the increased plasma lipid peroxidation and nitrotyrosine formation within the carotid body, and the enhanced carotid chemosensory and ventilatory responses to hypoxia, as well as heart rate variability alterations and hypertension. The present results support an essential role for oxidative stress in the generation of carotid body chemosensory potentiation and systemic cardiorespiratory alterations induced by intermittent hypoxia.

Evidence for histamine as a new modulator of carotid body chemoreception.

It has been proposed that histamine is an excitatory transmitter between the glomus cells of the carotid body (CB) and the nerve endings of the petrosal ganglion (PG) neurons. The histamine biosynthetic pathway and the presence of histamine H1, H2 and H3 receptors have been reported in the CB. Thus, histamine meets some of the criteria to be regarded as a transmitter. However, there is no evidence that glomus cells contain histamine, or whether its application produces chemosensory excitation. Therefore, we studied its immunocytochemical localization on cat CB and its effects on chemosensory activity. Using perfused and superfused in vitro CB and PG preparations, we assessed the effects of histamine hydrochloride on chemosensory discharges and of histamine H1, H2 and H3 receptor blockers. We found the presence of histamine immunoreactivity in dense-core vesicles in glomus cells. In an in vitro CB preparation we performed pharmacological experiments to characterize histamine effects. The application of histamine hydrochloride (0.5-1,000 microg) to the CB produces a dose-dependent increase in the carotid sinus nerve activity. The H1 receptor blockade with pyrilamine 500 nM produces partial decrease of the histamine-induced response, whereas the H2 receptor blockade (ranitidine 100microM) fail to abolish the histamine excitatory effects. Antagonism of the H3 receptor results in an increase in carotid body chemosensory activity. On the other hand, application of histamine to the isolated PG had no effect on the carotid nerve discharge. Our results suggest that histamine is a modulator of the carotid body chemoreception through H1 and H3 receptor activation.

Cardioventilatory acclimatization induced by chronic intermittent hypoxia.

It has been proposed that chronic intermittent hypoxia (CIH) contributes to generate hypertension in patients with obstructive sleep apnea syndrome and animal models, due to an enhanced sympathetic outflow. A possible contributing mechanism to the CIH-induced hypertension is a potentiation of carotid body (CB) chemosensory responses to hypoxia, but early changes that precede the CIH-induced hypertension are not completely known. Since the variability of heart rate (HRV) has been used as an index of autonomic influences on cardiovascular system, we studied the effects of short and long-term CIH exposure on HRV in animals with or without hypertension. In cats exposed to CIH (PO(2) approximately 75 Torr, 10 times/hr during 8 hr) for 4 days, the ventilatory response to acute hypoxia was potentiated, the arterial pressure remained unchanged, but the HRV power spectrum showed a shift towards the low frequency band. Exposure of rats to CIH (PO(2) approximately 37.5 Torr, 12 times/hr during 8 hr) for 12 days enhanced the ventilatory response to acute hypoxia, but did not increase the arterial pressure. After 21 days of CIH, we found a significant increase of arterial pressure and a shift of the HRV power spectrum towards the low frequency band. Thus, our results support the idea that hypertension induced by long-term CIH was preceded by alterations in the autonomic balance of HRV, associated with an enhance CB chemoreflex sensitivity to hypoxia. Therefore, few days of CIH are enough to enhance the CB reactivity to hypoxia, which contribute to the augmented ventilatory response to hypoxia, and to the early alterations in the autonomic balance of HRV.

Sexual behaviors and risk factors for HIV infection among men who have sex with men in the Dominican Republic.

OBJECTIVE: To describe self-reported types of sexual identity of men who have sex with men (MSM) in the Dominican Republic, assess sociodemographics and behavioral characteristics, and measure the prevalence of HIV-1 and syphilis. DESIGN: Cross-sectional study of MSM recruited from a variety of community settings. METHODS: A total of 354 men agreed to participate after giving verbal informed consent. Information was obtained using a standardized questionnaire assessing demographics and AIDS-relevant information. Blood was obtained for HIV and syphilis testing. RESULTS: Five main sexual identity groups emerged: cross dressers, homosexuals, gigolos, bisexuals and heterosexuals. Receptive anal and oral intercourse were commonly reported by men self-identifying as cross dressers or homosexuals, whereas nearly all of the remaining three groups practiced only insertive intercourse. Sexual contact with women was also commonly reported; overall, consistent condom use was infrequent. HIV antibodies were detected in 11.0% and serologic evidence of syphilis was found in 7.3%. Factors independently associated with HIV infection included serologic evidence of syphilis, having visited at least one of four local brothels in 1975-1985, and having had receptive anal intercourse with four or more partners in the last 12 months. CONCLUSIONS: Syphilis, sexual practices and social context of sex (commercial sex), rather than sexual identity per se, were associated with HIV infection. The complex social networks of MSM in this setting, the tendency to practice either insertive or receptive sex, but not both, infrequent condom use, high rates of syphilis and the frequency of sex with women need to be taken into account for targeted HIV prevention programs to be successful.

HIV-1 and HTLV-I in sexually transmitted disease clinics in the Dominican Republic.

A cross-sectional seroprevalence study of human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I) was undertaken among 494 attendees in two Santo Domingo sexually transmitted disease clinics in 1989. All participants were evaluated for Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and genital ulcers. Of the 494 participants, 15 (3.0%) were positive for HIV-1 and 14 (2.8%) were positive for HTLV-I. Twelve of 371 (3.2%) men were HIV-1 seropositive: 0 of 68 homosexual/bisexual and 12 (4.0%) of 302 heterosexual men (one seronegative male could not be classified). Three (2.4%) of 123 women were HIV-1 seropositive. One (1.5%) homosexual/bisexual man, five (1.7%) heterosexual men, and eight (6.5%) women were HTLV-I seropositive. Among heterosexual men, HIV-1 was associated with multiple lifetime sex partners (O.R. = 5.9; 95% C.I. = 1.4, 23; p = 0.007). HIV-1 was associated with genital ulcer disease among women (p = 0.004). Among women, HTLV-I was associated with professional sex work (O.R. = 18; 95% C.I. = 2.1, > 100; p = 0.001). These findings suggest the need for control of sexually transmitted diseases and targeted educational programs for prevention of HIV-1 and HTLV-I among individuals with high-risk behaviors in the Dominican Republic.

AIDS heterosexual predominance in the Dominican Republic.

AIDS surveillance data from the Dominican Republic are described for 1983-89. A positive serologic test for HIV was required, and standard clinical criteria were used for defining AIDS. There were 1,202 AIDS cases (820 men, 372 women, 10 of unknown gender) reported to the Ministry of Health, for a cumulative case rate of 17 per 100,000 persons. Rapid growth of the epidemic is noted, with 43% of the total cases reported in 1989. Heterosexual exposure accounts for 53% (593) of all cases, with a male-to-female ratio of 2.2:1, resembling a World Health Organization Pattern I/II country. Prevalence is highest in and surrounding the urbanized tourist areas of Santo Domingo and Puerto Plata and in districts with a high concentration of sugar plantation barracks, where laborers from Haiti and the Dominican Republic work and live. The distribution of AIDS cases is described by transmission exposure category, age, sex, year of diagnosis, and district. The National AIDS Surveillance Program can be improved by validation of exposure transmission categories through selected case investigation and by better reporting through training of health care providers. Surveillance data will assist in targeting future public health efforts to regions and persons at highest risk.