OBJECTIVES: The purpose of this study was to investigate the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotype and endothelial cell dysfunction or hypercoagulable state in elderly hypertensive patients. BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) polymorphism was recently reported to be associated with various cardiovascular diseases. However, the precise mechanism of this association remains unknown, and some confounding factors might also affect the association. Endothelial cell dysfunction and coagulation activation play important roles in both the atherosclerotic process and the onset of cardiovascular events. METHODS: We identified the ACE I/D genotype and measured the plasma levels of markers of endothelial cell damage (von Willebrand factor [vWF] and thrombomodulin) and of coagulation activation (prothrombin fragment F1 + 2 [F1 + 2]) in 318 asymptomatic elderly patients with hypertension, aged 59-93 years. RESULTS: The vWF level was significantly higher in those with the DD genotype (n = 54) than in those with the II genotype (n = 131, p < 0.0001) or with the ID genotype (n = 133, p < 0.0001). The TM levels were also higher in patients with the ID genotype (p < 0.005) and the DD genotype (p < 0.01) than in those with the II genotype. There were no differences in F1 + 2 level among the groups. Positive correlations of systolic blood pressure with levels of both vWF and thrombomodulin were found predominantly in patients with the II genotype (both p < 0.001), but no correlation was noted in those with the DD genotype. CONCLUSIONS: Considering the increased plasma levels of both endothelial cell-derived markers in the hypertensive patients with ACE DD genotype, we speculate that the ACE D allele is a risk factor for the development of hypertensive cardiovascular disease associated with endothelial cell damage.

Aged↗

PubMed1997

Malignant hyperthermia induced by general anesthesia for bone marrow harvesting.

We present a case of a bone marrow donor who developed rhabdomyolysis, acute renal failure and pulmonary edema following an apparently uneventful general anesthesia for bone marrow harvesting. Because malignant hyperthermia (MH) was suspected, he was treated with dantrolene, fluid loading, and continuous hemodiafiltration along with symptomatic supportive care. He made a full recovery and was discharged 3 weeks after harvest. Although the incidence of MH is low, marrow donation involves the risks of anesthesia as is seen in this case. Close monitoring is required to prevent life-threatening complications associated with the bone marrow harvesting procedure.

Adult↗

PubMed1996

Species specificity of anticoagulant activity of activated human protein C: involvement of factor V as well as protein S.

Activated protein C (APC) possesses species specificity in its anticoagulant activity. Human APC exerts only weak activity in rat plasma compared with that in human plasma. The present study was undertaken to estimate the difference in interaction of human and rat factors with human APC and to assess the cause of the species specificity. Human or rat protein S (PS), factor V, or factor VIII was used to supplement human plasma depleted of each respective factor, and the anticoagulant activity of human APC was measured in term of the elongation of activated partial thromboplastin time (APTT). The activity of human APC in rat PS- or factor V-supplemented plasma was weaker than that in the human PS- or factor V-supplemented plasma. Furthermore, using purified human and rat factor V, human APC showed weaker inactivation of rat factor V than human factor V. Equal anticoagulant activity was observed in human or rat factor VIII-supplemented plasma. And there was a little difference in the interaction of APC with its inhibitors in human or rat plasma during a few minutes of incubation as judged by measurement of residual activity by an enzyme capture assay. From these results factor V as well as PS seems to play a major role in the species specificity of APC.

Animals↗