Are the dynamic response characteristics of brachial artery flow-mediated dilation sensitive to the magnitude of increase in shear stimulus?

The purpose of this study was to determine the dynamic characteristics of brachial artery dilation in response to step increases in shear stress [flow-mediated dilation (FMD)]. Brachial artery diameter (BAD) and mean blood velocity (MBV) (Doppler ultrasound) were obtained in 15 healthy subjects. Step increases in MBV at two shear stimulus magnitudes were investigated: large (L; maximal MBV attainable), and small (S; MBV at 50% of the large step). Increase in shear rate (estimate of shear stress: MBV/BAD) was 76.8 +/- 15.6 s(-1) for L and 41.4 +/- 8.7 s(-1) for S. The peak %FMD was 14.5 +/- 3.8% for L and 5.7 +/- 2.1% for S (P < 0.001). Both the L (all subjects) and the S step trials (12 of 15 subjects) elicited a biphasic diameter response with a fast initial phase (phase I) followed by a slower final phase. Relative contribution of phase I to total FMD when two phases occurred was not sensitive to shear rate magnitude (r(2) = 0.003, slope P = 0.775). Parameters quantifying the dynamics of the FMD response [time delay (TD), time constant (tau)] were also not sensitive to shear rate magnitude for both phases (phase I: TD r(2) = 0.03, slope P = 0.376, tau r(2) = 0.04, slope P = 0.261; final phase: TD r(2) = 0.07, slope P = 0.169, tau r(2) = 0.07, slope P = 0.996). These data support the existence of two distinct mechanisms, or sets of mechanisms, in the human conduit artery FMD response that are proportionally sensitive to shear stimulus magnitude and whose dynamic response is not sensitive to shear stimulus magnitude.

Acceleration of the wavefront of myocardial necrosis by chronic hypertension and left ventricular hypertrophy in dogs.

Previous studies have shown that hypertension and left ventricular hypertrophy (HT-LVH) increase completed infarct size. Myocardial infarction progresses in a wavefront of myocardial necrosis from the subendocardium to the subepicardium. We tested two hypotheses: First, HT-LVH accelerates the wavefront of myocardial necrosis when compared with normotensive animals; and second, lowering of arterial pressure by infusing nitroprusside 1 hour after coronary artery occlusion exerts a salutary effect on infarct size. To test these hypotheses, systemic hypertension (mean aortic pressure = 141 +/- 3 mm Hg) and left ventricular hypertrophy (18% increase in left ventricular mass) were induced in dogs using a single-kidney, single-clip model. Seventeen adult mongrel dogs were used as controls. We measured mean aortic pressure, heart rate, left atrial pressure, and myocardial perfusion (microspheres) in several groups of normal and HT-LVH awake dogs. In two groups (normal and HT-LVH), 1 hour of circumflex coronary artery occlusion was followed by 4 hours of reperfusion. In two additional groups (normal and HT-LVH), 3 hours of circumflex coronary artery occlusion was followed by 90 minutes of reperfusion. In another group with HT-LVH, nitroprusside was infused to reduce mean arterial pressure to 100 mm Hg beginning 1 hour after occlusion and was continued for the duration of reperfusion period (HT-LVH + N). Infarct size was assessed using triphenyltetrazolium chloride stain and risk area was determined using postmortem barium angiography. Fifteen of 17 (88%) control animals survived coronary artery occlusion, whereas only 17 of 42 (40%) dogs with HT-LVH survived coronary occlusion (p less than 0.05). Infarct-to-risk ratios in the various layers of the left ventricular wall were determined for survivors in all groups. After 1 hour of coronary occlusion more than twice as much mid-wall and epicardium was infarcted in the HT-LVH group compared with the control group. After 3 hours of coronary occlusion significantly more endocardium, mid-wall, and epicardium was infarcted in the dogs with HT-LVH. In the nitroprusside-treated HT-LVH dogs, the infarct sizes were similar to control animals. From these data we conclude: 1) the rate of infarction is accelerated in animals with HT-LVH; 2) nitroprusside infused 1 hour after coronary artery occlusion and continued throughout the reperfusion period exerts beneficial effect on infarct size when compared with control animals; and 3) acute coronary artery occlusion in animals with HT-LVH is associated with significantly greater mortality when compared with control animals.

Measurement of left ventricular mass in vivo using gated nuclear magnetic resonance imaging.

Alterations of left ventricular mass occur in a variety of congenital and acquired heart diseases. In vivo determination of left ventricular mass, using several different techniques, has been previously reported. Problems inherent in some previous methods include the use of ionizing radiation, complicated geometric assumptions and invasive techniques. We tested the ability of gated nuclear magnetic resonance imaging to determine in vivo left ventricular mass in animals. By studying both dogs (n = 9) and cats (n = 2) of various sizes, a broad range of left ventricular mass (7 to 133 g) was examined. With a 0.5 tesla superconducting nuclear magnetic resonance imaging system the left ventricle was imaged in the transaxial plane and multiple adjacent 10 mm thick slices were obtained. Endocardial and epicardial edges were manually traced in each computer-displayed image. The wall area of each image was determined by computer and the areas were summed and multiplied by the slice thickness and the specific gravity of muscle, providing calculated left ventricular mass. Calculated left ventricular mass was compared with actual postmortem left ventricular mass using linear regression analysis. An excellent relation between calculated and actual mass was found (r = 0.95; SEE = 13.1 g; regression equation: magnetic resonance mass = 0.95 X actual mass + 14.8 g). Intraobserver and interobserver reproducibility were also excellent (r = 0.99). Thus, gated nuclear magnetic resonance imaging can accurately determine in vivo left ventricular mass in anesthetized animals.

Immunologic and coagulation disorders in chlorpromazine-treated patients.

The prevalence of immunologic and coagulation disorders in 75 schizophrenic patients treated with chlorpromazine or other antipsychotic drugs was evaluated. Four groups were studied: Group A, chlorpromazine treatment for more than 2 1/2 years; Group B, chlorpromazine and other antipsychotic drug treatment for more than 2 1/2 years; Group C, chlorpromazine treatment for less than 2 1/2 years; Group D, no chlorpromazine, but other antipsychotic drug treatment. Significant elevation of serum IgM and prolongation of partial thromboplastin time were noted in patients who had long-term chlorpromazine treatment. The latter was caused by a circulating inhibitor resembling that seen with systemic lupus erythematosus. There was a significant correlation between the IgM level versus chlorpromazine dose or duration of treatment and the partial thromboplastin time versus chlorpromazine dose or duration of treatment. In Groups A and B, 63% had a positive antinuclear antibody test (greater than or equal to 1:80), 40% had antibodies to native DNA, and 58% had antibodies to nucleoprotein. These antibodies were negative in the other groups. The percentages of T lymphocytes were below normal in 13 of 41 patients treated with chlopromazine. Twenty of 42 patients in Groups A and B, and none of 28 in Groups C and D had splenomegaly. This study indicates that most patients on long-term chlorpromazine treatment develop one or more immunologic abnormalities.