In 20 of 198 patients with hypertrophic cardiomyopathy, Doppler color flow imaging revealed diastolic paradoxic jet flow across the obliterated left ventricular apex toward the base that suggested the presence of a discrete apical chamber. This prospective study characterized echocardiographic, ventriculographic and scintigraphic findings in these patients, as well as their clinical features. Although echocardiography did not directly show the apical chamber in 13 of the 20 patients, left ventriculography always revealed a small apical outpouching separated from the major basal cavity. Systolic bulging of the apex was always followed by early diastolic shrinkage together with persistent cavity narrowing between the two chambers. After the systolic jet flow, the paradoxic jet flow lasted for 366 +/- 160 ms after aortic valve closure and always extended into the diastolic filling period. The maximal velocity of the paradoxic jet flow occurred during isovolumetric relaxation and the mean velocity was 2 +/- 0.8 m/s, indicating a higher diastolic pressure in the apical chamber than in the main ventricle. Compared with patients who manifested cavity obliteration alone, patients with a paradoxic jet flow more often developed systemic embolism (p less than 0.01), ventricular tachycardia (p less than 0.05) and thallium perfusion abnormalities localized to the apical region (p less than 0.01). Thus, paradoxic jet flow could be an important marker of concealed apical asynergy and the risk of adverse clinical events. The higher diastolic apical pressure suggested by the flow may contribute to the development of an apical aneurysm, even in the absence of fixed coronary artery disease.
Background-Carbon dioxide-rich water bathing has the effect of vasodilatation, whereas it remains undetermined whether this therapy exerts an angiogenic action associated with new vessel formation. Methods and Results-Unilateral hindlimb ischemia was induced by resecting the femoral arteries of C57BL/J mice.Lower limbs were immersed in CO 2 -enriched water (CO 2 concentration, 1000 to 1200 mg/L) or freshwater (control) at 37°C for 10 minutes once a day. Laser Doppler imaging revealed increased blood perfusion in ischemic limbs of CO 2 bathing (38% increase at day 28, PϽ0.001), whereas N G -nitro-L-arginine methyl ester treatment abolished this effect. Angiography or immunohistochemistry revealed that collateral vessel formation and capillary densities were increased (4.1-fold and 3.7-fold, PϽ0.001, respectively). Plasma vascular endothelial growth factor (VEGF) levels were elevated at day 14 (18%, PϽ0.05). VEGF mRNA levels, phosphorylation of NO synthase, and cGMP accumulation in the CO 2 -bathed hindlimb muscles were increased (2.7-fold, 2.4-fold, and 3.4-fold, respectively) but not in forelimb muscles. The number of circulating LinϪ/Flk-1ϩ/CD34Ϫ endothelial-lineage progenitor cells was markedly increased by CO 2 bathing (24-fold at day 14, PϽ0.001). The LinϪ/Flk-1ϩ/CD34Ϫ cells express other endothelial antigens (endoglin and VE-cadherin) and incorporated acetylated LDL. Conclusions-Our present study demonstrates that CO 2 bathing of ischemic hindlimb causes the induction of local VEGF synthesis, resulting in an NO-dependent neocapillary formation associated with mobilization of endothelial progenitor cells.
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