Biomedical subjects

M Jonas

Publications and source records attributed to M Jonas.

At least 19 recordsLinked to original sources

PubMed2000

Clinical profile and long-term prognosis of women < or = 50 years of age referred for coronary angiography for evaluation of chest pain.

A significant lack of information exists regarding risk factors, preventive strategies, diagnostic testing, and treatment of women with coronary artery disease (CAD), especially in the young age group. We studied the clinical profile, angiographic results, and long-term follow-up of 135 women aged < or =50 years referred for coronary angiography because of chest pain. The most prominent risk factor was hyperlipidemia (60%), followed by a family history of coronary disease (44%), systemic hypertension (40%), cigarette smoking (31%), postmenopausal state (23%), and diabetes mellitus (21%). Angiographically significant CAD was demonstrated in 79 of 135 patients (58%), most of whom (61%) had 1-vessel CAD. Women with compared to those without significant CAD had a higher prevalence of hyperlipidemia (71% vs 45%; p = 0.002) and of the post-menopausal state (30% vs 16%; p = 0.028). There was no difference in the incidence of positive noninvasive evaluation (ergometry or thallium scan) before catheterization between women with or without significant coronary lesions. At a follow-up period of 2 to 7 years, 3 women had acute myocardial infarction, all of whom demonstrated coronary lesions on prior angiography. No difference was found regarding the recurrence of chest pain on follow-up between women with or without significant CAD. Mortality and congestive heart failure were observed more frequently in women with CAD (6% vs 0%; p = 0.0516 and 12% vs 2%; p = 0.047, respectively).

Adult↗

PubMed2000

Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors.

Myelokathexis is a congenital disorder that causes severe chronic leukopenia and neutropenia. Characteristic findings include degenerative changes and hypersegmentation of mature neutrophils and hyperplasia of bone marrow myeloid cells. The associated neutropenia can be partially corrected by treatment with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These features led us to propose that accelerated apoptosis of neutrophil precursors might account for the neutropenic phenotype. Blood and bone marrow aspirates were obtained from 4 patients (2 unrelated families) with myelokathexis before G-CSF therapy and from 2 of the affected persons after G-CSF therapy (1 microg/kg per day subcutaneously for 3 weeks). Bone marrow was fractionated using immunomagnetic bead cell sorting into CD34(+), CD33(+)/CD34(-), and CD15(+)/CD34(-)/CD33(- )cell populations. Examination of these cells by flow cytometry and electron microscopy revealed abundant apoptosis in the CD15(+) neutrophil precursor population, characterized by enhanced annexin-V binding, extensive membrane blebbing, condensation of heterochromatin, and cell fragmentation. Colony-forming assays demonstrated significant reduction in a proportion of bone marrow myeloid-committed progenitor cells. Immunohistochemical analysis revealed a selective decrease in bcl-x, but not bcl-2, expression in the CD15(+)/CD34(-)/CD33(-)cell population compared with similar subpopulations of control bone marrow-derived myeloid precursors. After G-CSF therapy, apoptotic features of patients' bone marrow cells were substantially reduced, and the absolute neutrophil counts (ANC) and expression of bcl-x in CD15(+)/CD34(-)/CD33(-)cells increased. The authors concluded that myelokathexis is a disease characterized by the accelerated apoptosis of granulocytes and the depressed expression of bcl-x in bone marrow-derived granulocyte precursor cells. These abnormalities are partially corrected by the in vivo administration of G-CSF. (Blood. 2000;95:320-327)

Adult↗

PubMed2000

Pharmacological characterization of neurogenic responses of the sheep isolated internal anal sphincter.

The aim of the study was to establish the nature of the neurogenic responses of the sheep isolated anal sphincter. Isolated strips of sheep internal anal sphincter develop intrinsic contractile tone following the application of stretch tension. On transmural stimulation (1 - 20 Hz, 10 V pulse strength, 0.5 ms pulse width, 1 s every 180 s) transient relaxations were observed. The amplitude of the relaxations were frequency-dependent reaching a maximal response at 10 - 20 Hz and were inhibited by tetrodotoxin (0.3 microM). Neither atropine (0.3 microM) nor phentolamine (1 microM) affected control responses. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM) and the selective inhibitor of soluble guanylyl cyclase ODQ, (1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one) (1 microM) completely inhibited the neurogenic relaxations and uncovered contractions that were abolished by 1 microM phentolamine and 0.1 microM prazosin. The effect of L-NAME, but not that of ODQ, was partially reversed by the addition of L-arginine (1 mM). Sodium nitroprusside (10 nM - 10 microM) caused concentration-dependent inhibition of myogenic tone and this effect was significantly reduced by ODQ. Calcium-free Krebs-Henseleit solution also reduced myogenic tone by 85%. Transmural electrical stimulation of the sheep isolated internal anal sphincter causes a transient relaxation of myogenic tone that appears to involve nitric oxide from non-adrenergic, non-cholinergic nerves and, to a lesser degree, noradrenaline from sympathetic nerves. The characteristics of the preparation compares well with that of human tissue and may prove to be a suitable animal based model for further studies.

Anal Canal↗

PubMed1999

Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS).

The goals of this study were to determine whether the Fas-dependent apoptosis pathway is active in the lungs of patients with the acute respiratory distress syndrome (ARDS), and whether this pathway can contribute to lung epithelial injury. We found that soluble Fas ligand (sFasL) is present in bronchoalveolar lavage (BAL) fluid of patients before and after the onset of ARDS. The BAL concentration of sFasL at the onset of ARDS was significantly higher in patients who died. BAL from patients with ARDS induced apoptosis of distal lung epithelial cells, which express Fas, and this effect was inhibited by blocking the Fas/FasL system using three different strategies: anti-FasL mAb, anti-Fas mAb, and a Fas-Ig fusion protein. In contrast, BAL from patients at risk for ARDS had no effect on distal lung epithelial cell apoptosis. These data indicate that sFasL is released in the airspaces of patients with acute lung injury and suggest that activation of the Fas/FasL system contributes to the severe epithelial damage that occurs in ARDS. These data provide the first evidence that FasL can be released as a biologically active, death-inducing mediator capable of inducing apoptosis of cells of the distal pulmonary epithelium during acute lung injury.

Apoptosis↗

PubMed1999

Relation of early and one-year outcome after acute myocardial infarction to systemic arterial blood pressure on admission.

We evaluated whether elevated blood pressure (BP) levels with an acute myocardial infarction (AMI) affect the in-hospital course, short-term, and 1-year outcome. Data were derived from a nationwide survey of 2,212 consecutive patients with AMI. Patients were stratified into 3 groups according to admission BP levels: 1,320 patients had normal BP, 840 patients had high BP, and 52 patients had excessive BP. In-hospital (7 days) course, short-term (30 days), and 1-year outcome was compared between the groups. The 3 groups were similar with respect to age, but patients with excessive BP were more likely to be women and have a history of systemic hypertension and diabetes mellitus. The rate of thrombolytic therapy was similar among the 3 groups, but patients with excessively elevated BP were treated during hospitalization much more often with beta blockers, angiotensin-converting enzyme inhibitors, and diuretics. The incidence of stroke, transient ischemic attack, and bleeding complications were comparable in the 3 groups. In-hospital mortality was 5.0% , 4.0%, and 1.9% in the normal, high, and excessively elevated BP groups, respectively (p = 0.19). The short-term rehospitalization or mortality rate was similar among the 3 groups. The 1-year mortality rate was 12.3%, 14.1%, and 10.2% in the normal, high, and excessively elevated BP groups, respectively (p = 0.61). A multivariate logistic regression analysis yielded age, women, and Killip class > or = 2 as the only significant predictors of mortality during follow-up. Thus, with the current medical therapy, excessively elevated BP levels with AMI is not associated with a worse short-term or 1-year outcome.

Adrenergic beta-Antagonists↗

PubMed1999

Are coronary patients at higher risk with digoxin therapy? An ongoing controversy.

Previous reports have yielded contradictory conclusions regarding the safety of digoxin therapy in patients with acute myocardial infarction. The purpose of our study was to determine whether digoxin therapy is associated with increased mortality in patients with chronic coronary artery disease. We analyzed data from 8173 patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) trial and who survived an acute myocardial infarction at least 6 months prior to the study. Three-year overall mortality of the 451 (15.5%) patients receiving digoxin (according to the judgement of their treating physician) at the time of screening for BIP participation, was 22.4% compared to 8.3% in the patients who did not receive digoxin. Cardiac mortality was 16.2% in the digoxin-treated group, compared to 4.9% in the non-treated patients. The increased risk associated with digoxin remained statistically significant when patients were stratified according to sex, age groups, functional capacity and the presence of hypertension, diabetes or angina. The administration of digoxin to survivors of an acute myocardial infarction in the chronic phase of their disease, is statistically associated with a 30-50% increase in the risk of overall and cardiac mortality during long-term follow-up. A propensity of increased risk of arrhythmias in ischemic coronary patients may explain this finding.

Cardiotonic Agents↗

PubMed1999

Lateral internal sphincterotomy is not redundant in the era of glyceryl trinitrate therapy for chronic anal fissure.

Lateral internal sphincterotomy has been the standard treatment for chronic anal fissure, but fissure healing rates of up to 80% with topical glyceryl trinitrate (GTN) treatment have suggested that this operation may become redundant. We evaluated the results of topical treatment of chronic anal fissures with 0.2% GTN for 6 weeks in the outpatient clinical setting, outside the confines of a randomized clinical trial. The role of lateral internal sphincterotomy in the GTN era was also assessed. GTN induced fissure healing in 21 of 49 consecutive patients. Fissures healed spontaneously in 2 patients who discontinued GTN because of headache. Lateral internal sphincterotomy was performed in 26 patients who had persistent symptoms after 6 weeks of GTN therapy. At the 6-week post-sphincterotomy review, all fissures had healed and there were no complications. In this study topical GTN for treatment of chronic anal fissure in the outpatient setting was not as effective as demonstrated in controlled clinical trials. Lateral internal sphincterotomy is still a good therapeutic option, especially in patients not responding to GTN.

Adult↗

PubMed1998

Prognostic significance of cerebrovascular disease in 11,526 chronic coronary artery disease patients. Bezafibrate Infarction Prevention (BIP) Study Group.

Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality.

Aged↗

PubMed1998

Differentiation of cultured keratinocytes promotes the adherence of Streptococcus pyogenes.

Based on a consideration of the histopathology of nonbullous impetigo that shows localization of Streptococcus pyogenes to highly differentiated, subcorneal keratinocytes, we hypothesized that adherence of an impetigo strain of S. pyogenes would be promoted by terminal differentiation of keratinocytes. An assay was developed in which S. pyogenes adhered via pilus-like projections from the cell wall to the surface of cultured human keratinocytes in a time- and inoculum-dependent manner suggestive of a receptor-mediated process. Terminal differentiation of keratinocytes was induced by increasing the calcium concentration in the growth medium, and was confirmed by morphologic analysis using electron microscopy. Adherence of S. pyogenes was three and fourfold greater to keratinocytes differentiated in 1.0 and 1.5 mM calcium, respectively, compared with undifferentiated keratinocytes in 0.15 mM calcium. The presence of calcium during the adherence assay further enhanced adherence nearly twofold. Adherence occurred preferentially to sites of contact between adjacent keratinocytes, suggesting that the keratinocyte receptor may be a molecule involved in cell-to-cell adhesion. In contrast, nonpathogenic Streptococcus gordonii adhered poorly to keratinocytes regardless of their state of terminal differentiation, and adherence of a pharyngeal strain of S. pyogenes was twofold greater to undifferentiated than differentiated keratinocytes. This is the first report of in vitro adherence of S. pyogenes to keratinocytes in a manner that emulates human impetigo. Adherence of only the impetigo strain, and not the pharyngeal strain of S. pyogenes or the nonpathogenic S. gorgonii isolate, was promoted by keratinocyte differentiation. This result provides a model system for investigating the molecular pathogenesis of streptococcal skin infections.

Bacterial Adhesion↗

PubMed1998

Nifedipine and cancer mortality: ten-year follow-up of 2607 patients after acute myocardial infarction.

Recent publications contended that the use of short-acting calcium antagonists may double the risk of cancer incidence and possibly increase mortality in hypertensive patients. The purpose of this study was to assess the risk ratio for cancer mortality associated with nifedipine in a large population of patients post-myocardial infarction. Cancer mortality data, over a 10-year period, were obtained on 2607 hospital survivors of acute myocardial infarction who were screened, but not included, in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT I) study. In this group of patients, 526 (20%) were on nifedipine, according to their treating physicians' decision. In the cohort of screened patients not included in SPRINT I, there were 22 (4.2%) cancer-related deaths in the patients on nifedipine compared with 114 (5.5%) in the group not treated with nifedipine (P = 0.23). In multivariate analysis, the 10-year cancer mortality risk ratio associated with nifedipine therapy was 1.06 (95% CI 0.52-2.18). The current analysis shows no evidence of an increased risk of cancer mortality in a large number of patients treated at baseline with nifedipine.

Aged↗

PubMed1998

In vitro evaluation of a new lithium dilution method of measuring cardiac output and shunt fraction in patients undergoing venovenous extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate, in vitro, a method of measuring cardiac output and shunt fraction during venovenous extracorporeal membrane oxygenation (ECMO). DESIGN: Experimental study using an in vitro model. SETTING: A teaching hospital. MODEL: An ECMO circuit was set up in parallel with a patient circuit consisting of tubing through which saline was circulated from a 50-L reservoir by a pump which was set at 3 L/min to represent cardiac output. A second pump in the ECMO circuit drew saline from the patient circuit and passed it through a membrane oxygenator. The flow from the membrane oxygenator either returned directly to the patient circuit or was diverted, via a third pump, back into the ECMO circuit, thereby producing a shunt. INTERVENTIONS: By adjusting the flow rates of the second (ECMO) and third (shunt) pumps, three shunt fractions of 12%, 25%, and 50% were produced at three different ECMO flow rates. Lithium chloride (0.15 mmol) was injected just downstream of the membrane oxygenator; the lithium ion concentration-time curves were recorded simultaneously in the flow returning to the saline reservoir and in the flow just upstream of the membrane oxygenator using lithium selective electrodes. MEASUREMENTS AND MAIN RESULTS: Nine pairs of curves were recorded, one pair for each combination of ECMO and shunt flow rates. Analysis of these curves allowed shunt flow and "cardiac output" to be calculated and compared with the flow rates delivered by the pumps. Mean "cardiac output" derived from the lithium dilution curves was 2.98 +/- 0.18 (SD) L/min, compared with a delivered pump flow of 3 L/min. Measured shunt flow = 0.008 + 1.09 x actual shunt flow (R = 0.997). CONCLUSIONS: This method would allow cardiac output and shunt flow to be measured in patients undergoing venovenous ECMO. It could result in better patient management and improved cannula design.

Blood Flow Velocity↗

PubMed1998

Characterization of group B streptococcal invasion of human chorion and amnion epithelial cells In vitro.

Group B streptococci (GBS) have been cultured from the chorioamnionic membrane of pregnant women, usually in association with chorioamnionitis and premature labor (K. A. Boggess, D. H. Watts, S. L. Hillier, M. A. Krohn, T. J. Benedetti, and D. A. Eschenbach, Obstet. Gynecol. 87:779-784, 1996). Colonization and infection of placental membranes can be a prelude to neonatal GBS infections even in the presence of intact membranes (R. L. Naeye and E. C. Peters, Pediatrics 61:171-177, 1978), suggesting that GBS cause chorioamnionitis or establish amniotic fluid infections by partial or complete penetration of the placental membranes. We have isolated and grown cultures of primary chorion and amnion cells from human cesarean-section placentas. This has provided a biologically relevant model for investigating GBS adherence to and invasion of the two epithelial barriers of the placental membrane. GBS adhered to chorion cell monolayers to a high degree. Pretreatment of GBS with trypsin reduced adherence up to 10-fold, which suggested that the bacterial ligand(s) was a protein. GBS invaded chorion cells at a high rate in vitro, and invasion was dependent on cellular actin polymerization. GBS could be seen within intracellular vacuoles of chorion cells by transmission electron microscopy. We also demonstrated that GBS were capable of transcytosing through intact chorion cell monolayers without disruption of intracellular junctions. GBS also adhered to amnion cells; in contrast, however, these bacteria failed to invade amnion cells under a variety of assay conditions. GBS interactions with the chorion epithelial cell layer shown here correlate well with epidemiological and pathological studies of GBS chorioamnionitis. Our data also suggest that the amnion cell layer may provide an effective barrier against infection of the amniotic fluid.

Amnion↗

PubMed1998

The locus of tumor necrosis factor-alpha action in lung inflammation.

The pulmonary host response to infection and inflammation appears, at least in part, to be compartmentalized from the systemic host response. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in lung inflammation and injury, but its site(s) of action has not been clearly defined. To investigate this, transgenic mice (surfactant apoprotein C promotor/soluble TNF receptor type II-Fc fusion protein ([SPCTNFRIIFc] mice) were generated in which TNF-alpha was selectively antagonized in the distal lung through tissue-specific expression of sTNFRIIFc, a soluble TNF inhibitor. The lung inflammatory response in these mice to pulmonary challenge with Micropolyspora faeni antigen or lipopolysaccharide (LPS) was compared with the response of wild-type mice, wild-type mice treated with recombinant sTNFRIIFc intravenously, and type I TNF-receptor knockout mice. Recruitment of polymorphonuclear leukocytes (PMN) to the lung after challenge with M. faeni antigen was essentially abolished in the TNFRI knockout mice and markedly reduced in the SPCTNFRIIFc mice. Wild-type mice given sTNFRIIFc intravenously in amounts resulting in lung concentrations similar to those in SPCTNFRIIFc mice also showed significantly reduced lung PMN recruitment, whereas those given doses that achieved such concentrations in the blood but low levels in the lung did not. In contrast, PMN recruitment to the lung following aerosol challenge with LPS was reduced significantly in the TNFRI knockout mice and in mice given high-dose sTNFRIIFc intravenously, but was not reduced significantly in SPCTNFRIIFc mice. Thus, inhibition of PMN recruitment in response to M. faeni antigen correlated largely with the extent of intrapulmonary inhibition of TNF-alpha, whereas the response to LPS correlated best with the extent of extrapulmonary inhibition of TNF-alpha. These studies indicate that TNF-alpha may act at different loci to mediate lung inflammation, with the site of action depending in part on the nature of the inflammatory stimulus, and that SPCTNFRIIFc mice provide a tool by which the locus of TNF action can be addressed.

Administration, Intranasal↗

PubMed1997

Blockade of CD49d (alpha4 integrin) on intrapulmonary but not circulating leukocytes inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.

Immunized mice after inhalation of specific antigen have the following characteristic features of human asthma: airway eosinophilia, mucus and Th2 cytokine release, and hyperresponsiveness to methacholine. A model of late-phase allergic pulmonary inflammation in ovalbumin-sensitized mice was used to address the role of the alpha4 integrin (CD49d) in mediating the airway inflammation and hyperresponsiveness. Local, intrapulmonary blockade of CD49d by intranasal administration of CD49d mAb inhibited all signs of lung inflammation, IL-4 and IL-5 release, and hyperresponsiveness to methacholine. In contrast, CD49d blockade on circulating leukocytes by intraperitoneal CD49d mAb treatment only prevented the airway eosinophilia. In this asthma model, a CD49d-positive intrapulmonary leukocyte distinct from the eosinophil is the key effector cell of allergen-induced pulmonary inflammation and hyperresponsiveness.

Allergens↗

PubMed1997

Lithium dilution cardiac output measurement: a comparison with thermodilution.

OBJECTIVE: To compare the results of cardiac output measurements obtained by lithium dilution and thermodilution. DESIGN: Case series, observational study. SETTING: High-dependency postoperative unit and intensive care unit of a teaching hospital. PATIENTS: Forty patients were studied. Thirty-four patients had undergoing heart surgery requiring cardiopulmonary bypass within the previous 2 days; the diagnoses in the other patients were myocardial infarct (n = 2), septicemia (n = 2), adult respiratory distress syndrome, and pericardectomy. INTERVENTIONS: Cardiac output was measured five times in each patient, using lithium dilution (single measurement) and bolus thermodilution (series of three to six measurements according to standard clinical practice, taking the average of the closest three). In a subgroup of 14 patients, cardiac output was also measured using "continuous thermodilution." MEASUREMENTS AND MAIN RESULTS: Comparing lithium dilution with bolus thermodilution, the mean of the differences (lithium dilution-thermodilution) was -0.25 +/- 0.46 [SD] L/min. Linear regression analysis gave y = 0.31 + 0.89x (r2 = .94) for lithium dilution vs. thermodilution. CONCLUSIONS: The overall agreement between the two methods was good. The variability of the thermodilution measurements was greater than that of the lithium dilution measurements. The lithium dilution method is at least as accurate as bolus thermodilution and, since pulmonary artery catheterization is not needed, it has the advantages of being safe and quick to perform.

Adult↗

PubMed1997

Invasion of brain microvascular endothelial cells by group B streptococci.

Group B streptococci (GBS) are the leading cause of meningitis in newborns. Although meningitis develops following bacteremia, the precise mechanism or mechanisms whereby GBS leave the bloodstream and gain access to the central nervous system (CNS) are not known. We hypothesized that GBS produce meningitis because of a unique capacity to invade human brain microvascular endothelial cells (BMEC), the single-cell layer which constitutes the blood-brain barrier. In order to test this hypothesis, we developed an in vitro model with BMEC isolated from a human, immortalized by simian virus 40 transformation, and propagated in tissue culture monolayers. GBS invasion of BMEC monolayers was demonstrated by electron microscopy. Intracellular GBS were found within membrane-bound vacuoles, suggesting the organism induced its own endocytic uptake. GBS invasion of BMEC was quantified with a gentamicin protection assay. Serotype III strains, which account for the majority of CNS isolates, invaded BMEC more efficiently than strains from other common GBS serotypes. GBS survived within BMEC for up to 20 h without significant intracellular replication. GBS invasion of BMEC required active bacterial DNA, RNA, and protein synthesis, as well as microfilament and microtubule elements of the eukaryotic cytoskeleton. The polysaccharide capsule of GBS attenuated the invasive ability of the organism. At high bacterial densities, GBS invasion of BMEC was accompanied by evidence of cellular injury; this cytotoxicity was correlated to beta-hemolysin production by the bacterium. Finally, GBS demonstrated transcytosis across intact, polar BMEC monolayers grown on Transwell membranes. GBS invasion of BMEC may be a primary step in the pathogenesis of meningitis, allowing bacteria access to the CNS by transcytosis or by injury and disruption of the endothelial blood-brain barrier.

Brain↗

PubMed1997

Elevated levels of serum creatine kinase induced by hyponatraemia.

Elevated serum creatine kinase levels are one of the major criteria for the diagnosis of myocardial injury. Noncardiac causes such as muscular and brain damage may also be associated with elevated serum creatine kinase levels. Hyponatremia may induce increased serum creatine kinase in association with rhabdomyolysis or with hypothyroidism. A patient is described where three episodes of hyponatraemia not associated with rhabdomyolysis or hypothyroidism induced transient elevations of serum creatine kinase levels. The association between hyponatraemia and elevated creatine kinase levels should be emphasized to prevent erroneous diagnosis of myocardial injury.

Aged↗

PubMed1997

Time course of the human pulmonary vascular response to 8 hours of isocapnic hypoxia.

To examine the hypothesis that the human pulmonary vascular response to hypoxia has a component with a slow time course, we measured pulmonary vascular resistance (PVR) in six healthy adult males during 8 h of isocapnic hypoxia. A balloon-tipped pulmonary artery catheter with thermistor was introduced via a forearm vein and used to derive PVR. The subjects were seated in a chamber in which the oxygen and carbon dioxide concentrations were adjusted to maintain an end-tidal Po2 of 50 Torr and an end-tidal Pco2 equal to the subject's normal prehypoxic value. PVR was measured before and at 0.5-h intervals during 8 h of hypoxia, the following 3 h of isocapnic euoxia (end-tidal Po2 100 Torr), and a subsequent 1-h reexposure to hypoxia. PVR rose from 1.23 +/- 0.26 (SE) Torr-min.1(-1) under euoxia [time (t) = 0] to 1.77 +/- 0.21 Torr.min.1(-1) at t = 0.5 h, reached a maximum at 2 h (2.91 +/- 0.33 Torr.min.1(-1)), and remained fairly constant between 2 and 8 h. Restoration of euoxia at 8 h led to a reduction in PVR with a slow component. Reexposure to hypoxia at 11 h resulted in a greater increase in PVR than at 1 h. Systemic vascular resistance had a similar slow component to its response, falling from 18.6 +/- 1.3 Torr.min.1(-1) at t = 0 to 17.3 +/- 1.4 Torr.min.1(-1) at t = 0.5 h, 14.4 +/- 0.6 Torr.min.1(-1) at t = 4 h, and 13.8 +/- 0.8 Torr.min.1(-1) at t = 8 h. The human pulmonary and systemic vascular responses to hypoxia extend over at least several hours.

Adult↗