More about the "ARB MI paradox"

"Logic dictates that angiotensin converting enzyme inhibitors should remain the preferred drug across the entire spectrum of cardiometabolic disease"     

Direct observation of the "oxygen paradox" in single rat ventricular myocytes

By phase contrast microscopy with video length tracking, we followed the sequence of morphological changes in individual isolated rat ventricular myocytes during anoxia followed by reoxygenation. Cells appeared normal during early anoxia. After a duration of anoxia T1, which varied from 17-47 minutes in different cells, each cell abruptly contracted an average of 33% in length to an inert rectangular form presumed to be a rigor state. Cells which were reoxygenated before the onset of rigor showed normal morphology and an unchanged extent of shortening on field stimulation, compared to control. Cells that were reoxygenated after a time in the rigor state, T2, either partially recovered to a shortened rectangular form capable of stimulated twitches or rounded up rapidly to a disordered hypercontracture form. The distribution of T1 was the same for cells which recovered and which hypercontracted. In contrast, the outcome of reoxygenation depended markedly on T2: all cells that were reoxygenated after less than 10 minutes of rigor recovered function, whereas all cells that spent more than 20 minutes in rigor hypercontracted when reoxygenated. The hypercontracture appears to be the cellular analog of the "oxygen paradox" in whole hearts. Its occurrence is reliably related to duration of rigor state but not to duration of hypoxia, because of marked cellular variability in the time of onset of rigor.     

Cobalt, manganese and the calcium paradox

The reperfusion of hearts with Ca2+-containing buffers after relatively short periods of Ca2+-free perfusion results in tissue damage, Ca2+ overload, loss of mechanical function and displacement of intracellular components into the extracellular phase. Using isolated, spontaneously beating Langendorff perfused rat hearts we have investigated whether Mn2+ and Co2+ exert a dose dependent inhibitory effect on this gain in Ca2+ and loss of intracellular constituents (assayed as myoglobin). We have also determined if the timing of the addition of Co2+ or Mn2+ is critical, and whether their protective effect is Ca2+-sensitive. When added only at Ca2+ repletion neither Co2+ nor Mn2+ provided protection. When present during the entire period of Ca2+ depletion and repletion, Mn2+ (005 to 4.0 mM) and Co2+ (0.1 to 4.0 mM) exerted a dose-dependent protective effect, indicted by a reduced and delayed onset of myoglobin release, a reduced gain in Ca2+, and an improved recovery of mechanical function. This protection was proportionally diminished if the cations were added late during the 10 min period of Ca2+ depletion and further reduced if after their late addition, Mn2+-free or Co2+-free Ca2+ repletion buffer was used. Mn2+ was more effective than Co2+, and decreasing the Ca2+ content of the perfusion buffer from 2.5 to 1.3 mmol.1-1 shifted the dose-response curve for this protection to the left. These results are discussed in terms of the possible mechanisms involved in the dose and time dependent protective effect of Mn2+ and Co2+.     

Cigarettes, respiratory rate, and the relaxation paradox

Recent research indicates that individuals differ in their physiological reactions to nicotine, some showing strong increases in heart rate within 1 min of beginning to smoke and others showing little or no heart rate change with smoking. In the present research, monitoring of the respiratory rates of these two types of smokers before, during, and after smoking revealed that the former show an increase in respiratory rate while smoking, whereas the latter show a decrease. It is suggested that these changes in respiratory rate, a relatively easily monitored bodily function, may provide the cues used by smokers for inferring the effect that smoking has on them, that is, stimulating versus relaxing.     

Alcohol,ischemic heart disease,and the french paradox

Many studies have shown either an inverse relation between alcohol intake and ischemic heart disease or a U-shaped curve in which the equivalent of two drinks per day of any kind of alcohol is associated with a decreased incidence of coronary disease compared with no drinks, while higher doses result in an increased risk of infarction and stroke. Although the cardioprotective effects of most alcoholic beverages are probably due to an elevation of high-density lipoprotein as well as the ability of alcohol to prevent platelet aggregation and increased fibrinolysis, there is an increased favorable effect of red wine. The unique cardioprotective properties of red wine reside in the action of flavonoids which are absent in white wine (with the exception of champagne) and sparse in beer (with the exception of dark beers). The best researched flavonoids are resveritrol and quercetin, which confer antioxidant properties more potent than alpha-tocopherol. Grape juice has about half the amount of flavonoids by volume as does red wine.     

"Smoker's paradox" in patients with acute myocardial infarction receiving primary coronary intervention

OBJECTIVES: Smokers with acute myocardial infarction have lower mortality rates than non-smokers despite increased risk for coronary artery disease. This study assessed the effects of smoking on complications and outcomes after acute myocardial infarction, and investigated the relationship between the clinical factors and the paradoxical effects of smoking in patients receiving primary coronary intervention. METHODS: Subjects were 367 consecutive patients with acute myocardial infarction who were admitted within 24 hr of onset and underwent successful coronary intervention, 165 (45%) of whom were smokers. RESULTS: The smoking group contained significantly more male patients, and the smoking group was significantly younger than the non-smoking group (p < 0.0001). The value of acute phase brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were significantly lower (BNP: 250 +/- 366 vs 448 +/- 513pg/ml, p = 0.0002; ANP: 48 +/- 77 vs 74 +/- 82pg/ml, p = 0.005) in the smoking group. Peak creatine kinase time from onset was significantly earlier (12.9 +/- 9.3 vs 16.1 +/- 10.0 hr, p = 0.049) in the smoking group. Left ventricular ejection fraction in the chronic phase was significantly better in the smoking group (58 +/- 13% vs 52 +/- 14%, p = 0.03). The early ST-segment resolution rate was higher in the smoking group (81% vs 67%, p = 0.003), and there were significantly fewer patients with heart failure in the smoking group than in the non-smoking group (28% vs 41%, p = 0.01). The cardiac mortality rate during 6 months was significantly lower in the smoking group (3% vs 9%, p = 0.01). The beneficial effects of smoking on the prognosis were related with the differences in sex and age of the study group. CONCLUSIONS: The reason why smokers with acute myocardial infarction have lower mortality rates than non-smokers, the "smoker's paradox", may be related to less damage to the microvascular function after primary coronary intervention, with lower BNP and better left ventricular ejection fraction.     

HIV,transmitted drug resistance,and the paradox of preexposure prophylaxis

The administration of antiretrovirals before HIV exposure to prevent infection (i.e., preexposure prophylaxis; PrEP) is under evaluation in clinical trials. Because PrEP is based on antiretrovirals, there is considerable concern that it could substantially increase transmitted resistance, particularly in resource-rich countries. Here we use a mathematical model to predict the effect of PrEP interventions on the HIV epidemic in the men-who-have-sex-with-men community in San Francisco. The model is calibrated using Monte Carlo filtering and analyzed by constructing nonlinear response hypersurfaces. We predict PrEP interventions could substantially reduce transmission but significantly increase the proportion of new infections caused by resistant strains. Two mechanisms can cause this increase. If risk compensation occurs, the proportion increases due to increasing transmission of resistant strains and decreasing transmission of wild-type strains. If risk behavior remains stable, the increase occurs because of reduced transmission of resistant strains coupled with an even greater reduction in transmission of wild-type strains. We define this as the paradox of PrEP (i.e., resistance appears to be increasing, but is actually decreasing). We determine this paradox is likely to occur if the efficacy of PrEP regimens against wild-type strains is greater than 30% and the relative efficacy against resistant strains is greater than 0.2 but less than the efficacy against wild-type. Our modeling shows, if risk behavior increases, that it is a valid concern that PrEP could significantly increase transmitted resistance. However, if risk behavior remains stable, we find the concern is unfounded and PrEP interventions are likely to decrease transmitted resistance.     

肥胖矛盾现象

肥胖是目前全球面临的重大公共卫生问题之一.肥胖既是多种心血管疾病与代谢病的主要危险因素,也是重要的致病因子.但是,近年来,一些横断面分析和回顾性研究发现,体质指数与心血管预后及靶器官损害呈负相关,有学者将这种现象称为＂肥胖矛盾＂.