Exercise in a healthy heart program: a cohort study.

OBJECTIVE: To assess the effects of exercise on resting heart rate (RHR), weight, lipid profile, and blood pressure. We hypothesized that the participants who increased their physical activity would show improvement in their cardiovascular risk factors compared to those who did not. DESIGN: Retrospective chart review over the mean duration of 4.9 years of follow-up. SETTING: Healthy Heart Program Prevention Clinic at St. Paul's Hospital, Vancouver, British Columbia, Canada. PARTICIPANTS: We reviewed 300 charts of patients randomly selected from those who attended the Prevention Clinic between 1984 and 2009. 248 (82.7%) patients were referred for primary prevention and 52 (17.3%) for secondary prevention. PRIMARY AND SECONDARY OUTCOME MEASURES: Weight, RHR, lipid profile, and blood pressure were recorded at the initial and last visit. RESULTS: During a mean of 4.9 years of follow-up, 55% of participants improved their exercise. The mean decrease in the RHR for these patients (group 1) was 5.9 beats per minute (bpm) versus the mean increase of 0.3 bpm for the "no change" group (group 2) (P < 0.01). The mean net weight increase in group 1 was 0.06 kg/year versus 0.25 kg/year in group 2. Because of medications, all patients had a significant improvement in their lipid profiles. Furthermore, there was a statistically significant greater reduction in Framingham Risk Score (FRS) in group 1 versus group 2 (11.8% versus 15.1%, P < 0.01). CONCLUSION: Participation in the program significantly reduces modifiable risk factors for cardiovascular disease. Improved exercise regimen results in lower RHR and greater reduction in FRS. However, even in a Prevention Program, despite strong advocacy of the importance of exercise, a significant percentage of participants does not improve their exercise habits.

Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells.

BACKGROUND AND OBJECTIVE: Epidemiological and animal studies suggest that periodontal infections increase atherosclerosis risk. Periodontitis patients have elevated levels of anti-phosphorylcholine (anti-PC) reactive not only with numerous periodontal organisms but also with minimally modified low-density lipoprotein (mmLDL). Dendritic cells (DCs) reside in arterial walls and accumulate in atherosclerotic lesions. The ability of anti-PC to bind mmLDL prompted the hypothesis that opsonized mmLDL would stimulate DCs and enhance the production of proinflammatory cytokines that promote atherogenic plaque development. MATERIAL AND METHODS: Monocyte-derived DCs (mDCs) were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, then stimulated with mmLDL or with anti-PC-opsonized mmLDL. The anti-PC effect was determined using flow cytometry, cofocal microscopy and cytokine assays. The production of CD83, IL-12p35 mRNA, IL-12p40 mRNA, IL-12p70 and IL-10 by DCs was monitored. RESULTS: Dendritic cells stimulated with mmLDL expressed little CD83 and produced little IL-12p70. However, anti-PC-opsonized mmLDL enhanced DC maturation, as indicated by upregulated CD83 and rapid (≤ 48 h) production of IL-12p70 if a source of interferon-γ (IFN-γ) was available. In leukocyte cultures, natural killer (NK) cells rapidly produced IFN-γ (≤ 48 h) when interacting with IL-12-producing DCs activated by anti-PC-opsonized mmLDL. Moreover, IFN-γ promoted DC IL-12 responses that were further augmented when mmLDL was opsonized with anti-PC. CONCLUSION: Minimally modified LDL-stimulated DCs and NK cells were mutually stimulatory, with DC IL-12p70 needed by NK cells and with NK cell IFN-γ needed by DCs. Moreover, production of these proinflammatory cytokines was markedly enhanced when LDL was opsonized by anti-PC. In short, the data suggest that the elevated anti-PC levels in periodontitis patients could promote a mechanism that facilitates atherosclerosis.

The effect of low molecular weight dextran on haemodynamics and respiratory function during endotoxin-induced shock.

The effects of low molecular weight dextran (LMWD) infusion, on gas exchange and haemodynamics were evaluated in sheep during endotoxin shock. The infusion of LMWD was started after signs of shock and lung injury were evident. After a stabilization period 10 micrograms kg-1 E. Coli endotoxin was infused i.v.. Endotoxin infusion resulted in an marked increase in pulmonary artery pressure (PAP) and decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2l). After 3 h MAP, PaO2, DO2l and compliance improved significantly in LMWD treated animals. The PAP had also decreased significantly in the LMWD-treated animals, but remained high in the controls (P less than 0.01). It was concluded that LMWD infusion improves haemodynamics and gas-exchange in sheep during endotoxin shock.

The role of low molecular weight dextran on platelet pulmonary trapping during endotoxin-induced shock.

In vivo behaviour of Indium-111-labelled platelets were followed simultaneously in the lungs, liver, spleen and kidneys in 16 adult sheep which were exposed to intravenous injection of endotoxin (10 micrograms/kg body wt.). The effects on the respiratory function and the central hemodynamics were also followed. Eight sheep received, 30 min after the endotoxin challenge, continuous intravenous infusion of low molecular weight dextran during 4 h while the other eight animals served as controls. A marked pulmonary and hepatic platelet sequestration was observed during and just after the endotoxin infusion and was followed by a marked platelet disaggregation within 30 min in both the groups. Three hours after the endotoxin a second wave of platelet sequestration occurred in the control animals, both in the lungs and in the liver, but no such increase was seen in the low molecular weight dextran-treated group. Within the kidneys only minor changes occurred during the experiment period. In the spleen, however, there was a decrease in platelet sequestration after endotoxin in both groups. Less marked hemodynamic and respiratory alterations occurred in the dextran-treated group compared to the controls. It was concluded that low molecular weight dextran decreases sequestration of platelets in the lungs and in the liver of sheep during endotoxic shock.

Early and late platelet sequestration in different organs during endotoxic shock.

Using a sheep model, platelet sequestration in lungs, liver, kidney, spleen, and brain was studied after the injection of Indium-111-oxine-labeled platelets and E. coli lipopolysaccharide. Immediately following endotoxin-induced shock, platelet sequestration was observed in lungs, liver, and kidney with corresponding decrease in measured Indium-111-oxine platelets in spleen and circulating blood. There was also a decrease in platelet counts as measured in a phase contrast microscope. The early platelet sequestration in lung, liver, and kidney was followed by platelet disaggregation and another phase of platelet sequestration which continued until the death of the animal. No platelet sequestration was observed in the brain.

Volumetric measurements in endotoxic shock using single photon emission tomography (SPET).

In 25 sheep organ volumes were determined using single photon emission tomography (SPET) prior to and during early endotoxic shock. The tracer used was in vitro 99Tcm-labelled red blood cells. The comparisons between the SPET volumes with the different lower threshold (LT) settings and the 'true' weighed organ volumes were done. The correlation coefficient of -0.87 was found between the LT and the 'true' liver volume and same for the spleen was -0.87. The LT-volume correction curves were used to determine the correct SPET volumes. Thus the accuracy of the liver volume lies within +/- 8%, the splenic volume within +/- 13% and that for the kidney volume +/- 19%. A highly significant decrease of the splenic volume was found 1 h after the induction of endotoxic shock, from 178 +/- 55 ml (mean +/- S.D.) to 101 +/- 25 ml. The kidney volume also decreased from 102 +/- 28 to 78 +/- 19 ml (p less than 0.05), whereas the liver volume remained nearly unchanged (796 +/- 219 versus 761 +/- 165 ml). The SPET study allows measurement of the organ volumes in vivo and the results are reliable when compared to the 'true' volumes. However, the proper LT-settings for organ contour are volume dependent and must be taken into account.

Cerebral circulation during endotoxic shock with special emphasis on the regional cerebral blood flow in vivo.

Left hemispheric blood flow was measured in eight adult Australian sheep prior to and, 1, 4, 30 and 60 min after the injection of endotoxin, E. Coli, 3 mg kg-1 bodyweight, using a radioisotope method. The mean left hemispheric blood flow prior to septic shock was 200 ml min-1 from which it rapidly reduced to 86 ml min-1 (1 min), and after a short recovery gradually decreased to 39 ml min-1 (60 min). Regional cerebral blood flow showed the highest value in the occipital region prior to septic shock, whereas 60 min after the endotoxin administration it reduced to the same low flow level, as in the other areas of the brain.

A radionuclide model for studying changes in the regional blood volumes during early endotoxic shock: an experimental model.

Septic shock constitutes a great threat to patients undergoing major abdominal surgery and also to trauma patients. The current state of knowledge on pathophysiological mechanisms in septic shock is not fully known. The aim of this study was to develop an experimental model that resembled the clinical situation and allowed the exploration of central and peripheral vascular mechanisms in endotoxic shock. Seven anesthetized sheep (weighing 30-45 kg) were provoked to lethal endotoxic shock by intravenous injection of 3 mg/kg bodyweight Escherichia coli endotoxin. The arterial pressure was monitored. Serial radionuclide images of the chest and abdomen were recorded after injecting technetium-99m-labeled RBC's. The volumetric (blood) alterations of liver, spleen, kidney, heart, and lungs, as well as peripheral muscle were measured. Prior to injection of endotoxin base-line data were obtained. Two to 4 minutes after injection, spleen volume decreased by -36% (mean) followed by a slow restoration; the left ventricular volume and kidneys increased by a maximum of 10-15%, while the liver volume increased by 38% of initial volume.

Assessment of cardiopulmonary alterations in endotoxic shock.

Using radionuclide first-pass technique, seven sheep were studied prior to and during endotoxic shock. In vitro labeled 99mTC red blood cells were used to measure right and left ventricular ejection fractions (RVEF and LVEF) and cardiopulmonary transit time (CPTT) prior to and at 1, 4, 30, and 60 minutes after the intravenous injection of endotoxin Escherichia coli, 3 mg/kg bodyweight. The LVEF decreased slightly from 51 to 42% but became normal four minutes later, while the RVEF remained decreased from 49 to 26% for 60 minutes. The CPTT was prolonged from 13 to 26 cardiac beats. The decrease in RVEF was well correlated with the prolongation of the CPTT.