A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study.
(41/956)
OBJECTIVES: The purpose of this study was to compare the effect of different antihypertensive agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretic agents on endothelial function. BACKGROUND: Endothelial dysfunction is a component of essential hypertension, and various antihypertensive drugs may be able to restore normal function. METHODS: Forearm blood flow (FBF) was measured in 296 patients with essential hypertension, including 46 untreated subjects using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin (NTG). Forty-seven normotensive subjects were similarly evaluated as control subjects. RESULTS: The FBF during reactive hyperemia in the 296 hypertensive patients was significantly less than that in age-matched normotensive subjects. The increase in FBF after administration of sublingual NTG was similar in both groups. Systolic and diastolic blood pressures and forearm vascular resistance were greater in the untreated group than in the four treated groups and did not differ with respect to the antihypertensive agent used. The maximal FBF response from reactive hyperemia was significantly greater in the ACE inhibitor-treated group than in the group treated with calcium antagonists, beta-blockers, diuretic agents, or nothing (40.5 +/- 5.2 vs. 32.9 +/- 5.8, 34.0 +/- 5.6, 32.1 +/- 5.9, and 31.9 +/- 5.8 ml/min per 100 ml tissue, p < 0.05, respectively). Reactive hyperemia was similar in the calcium antagonist, beta-blocker, diuretic and untreated groups, and changes in FBF after sublingual NTG administration were similar in all groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of reactive hyperemia in hypertensive patients treated with ACE inhibitors. CONCLUSIONS: These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO. (+info)
The transepidermal oxygen flux from the environment is in balance with the capillary oxygen supply.
(42/956)
It has been known since the nineteenth century that oxygen is taken up by the human skin. With a newly developed sensor it became possible to examine the influence of the vascular supply on the oxygen flux into the skin, tcJ(O2). tcJ(O2) was measured optically by determining the oxygen partial pressure difference, DeltapO2 across a diffusion test membrane, which itself was brought into close contact to the skin surface. Under these conditions DeltapO2 is proportional to the tcJ(O2). The skin perfusion was varied by the application of a hyperemizing ointment on the abdomen of 12 volunteers and by suprasystolic occlusion at the thigh of 20 volunteers. The tcJ(O2) was measured at a temperature of 33 degrees C of the humid skin. It was compared with the skin perfusion monitored by laser Doppler flow, and the capillary oxygen supply measured by transcutaneous partial pressure of oxygen, tcpO2, at an electrode temperature of 37 degrees C. The transcutaneous O2 flux produced a distinct DeltapO2 of 81.8 +/- 8.2 Torr (abdomen) and 72.8 +/- 12.3 Torr (ankle). In hyperemic skin on the abdomen the O2 flux was reduced (DeltapO2 = 57.7 +/- 10.6 Torr). The tcpO2 increased from 8.7 +/- 10.7 to 35.1 +/- 16.9 Torr. During suprasystolic occlusion, DeltapO2 increased by 6.4 +/- 2.3 Torr, whereas laser Doppler flow and tcpO2 decreased significantly. These results indicate that the total oxygen supply of the epidermis and the upper dermis is guaranteed even if the perfusion varies. (+info)
7-Nitroindazole impedes erythrocyte flow response to isovolemic hemodilution in the cerebral capillary circulation.
(43/956)
The role of nitric oxide (NO) in the mechanism of hemodilution-induced cerebral hyperemia is unclear. Based on findings in hypoxemia, the authors hypothesize that NO of neuronal origin contributes to an increase in velocity of erythrocytes in the cerebral microcirculation during anemia produced by isovolemic hemodilution. The change in erythrocyte velocity in cerebrocortical capillaries was assessed by intravital fluorescence video microscopy. A closed cranial window was implanted over the frontoparietal cortex of barbiturate-anesthetized, ventilated adult rats. Erythrocytes were labeled in vitro with fluorescein isothiocyanate and infused intravenously, and their velocity in subsurface capillaries was measured by frame-to-frame image tracking. Arterial blood was withdrawn in increments of 2 mL and replaced by serum albumin; arterial blood pressure was maintained at control level with an infusion of methoxamine. Erythrocyte velocity increased progressively, reaching 215% of baseline, as arterial hematocrit was reduced from 45% to 17%. Pretreatment of a separate group of rats with 7-nitroindazole (20 mg/kg intraperitoneally), a relatively selective inhibitor of neuronal NO synthase, abolished the increase in velocity at hematocrits greater than 20%, but the maximum velocity attained at the lowest hematocrit was similar to that in the control group. The results suggest that NO from neuronal source may contribute to the increase in capillary erythrocyte flow during moderate isovolemic hemodilution. (+info)
Effects of target-controlled infusion of propofol on the transient hyperaemic response and carbon dioxide reactivity in the middle cerebral artery.
(44/956)
The transient hyperaemic response (THR) of blood flow velocity in the middle cerebral artery (vmca), measured by transcranial Doppler ultrasonography (TCD), can be used to assess cerebral autoregulation. We have studied the effects of propofol administered by target-controlled infusion on vmca, THR and carbon dioxide reactivity. We studied 20 healthy adult patients undergoing elective surgery. A standardized anaesthetic comprising alfentanil 10 micrograms kg-1, propofol via a target-controlled infusor and vecuronium 0.1 mg kg-1 was used in both parts of the study. In the first part, THR tests were performed on 10 subjects while awake and then at an 'induction' target concentration of propofol (the target at which consciousness was lost, mean 6.7 (SD 1.1) micrograms ml-1). In the carbon dioxide study, reactivity was tested in 10 patients while awake and at the 'induction' target concentration of propofol by altering the end-tidal carbon dioxide partial pressure by 1 kPa either side of baseline. Propofol caused a significant decrease in vmca but indices of autoregulation, THR ratio and strength of autoregulation increased significantly. Propofol had no effect on carbon dioxide reactivity. These results suggest that propofol may have a beneficial effect on cerebral haemodynamics. (+info)
Postischemic vasodilation, endothelial activation, and cardiovascular remodeling in end-stage renal disease.
(45/956)
BACKGROUND: Cardiovascular complications are the major cause of death in end-stage renal disease (ESRD) patients. These complications are associated with concomitant cardiac and vascular remodeling, including left ventricular (LV) hypertrophy and hypertrophy of arterial walls. The endothelium influences the process of arterial remodeling. ESRD patients are characterized by the development of both cardiovascular remodeling and endothelial dysfunction. METHODS: Common carotid artery (CCA) intima-media thickness (IMT), CCA diameter, CCA distensibility, LV mass, and function were determined in 60 stable ESRD patients on hemodialysis and 34 age-, sex-, and blood pressure (BP)-matched controls, and their relationships with endothelial alterations were estimated by forearm postischemic vasodilation [flow debt repayment (FDR)] measured by venous plethysmography. We also evaluated the relationships between FDR and several cardiovascular risk factors or markers of inflammatory response or endothelial activation, for example, duration of dialysis, BP, smoking habits, cholesterol, parathormone (PTH), serum albumin, plasma fibrinogen, C-reactive protein (CRP), plasma homocysteine, plasminogen activator inhibitor (PAI-1), and von Willebrand factor (vWF). RESULTS: ESRD patients had increased LV mass, CCA diameter and CCA IMT, and had decreased CCA distensibility (P < 0.05). While the postischemic peak flow was comparable in controls and ESRD patients (29.2 +/- 9.1 vs. 27.9 +/- 0.2 mL/100 mL/min), FDR was lower in ESRD patients (116 +/- 31 vs. 88 +/- 32%, P < 0.001) because of the shorter duration of vasodilation (127 +/- 36 vs. 96 +/- 32 s, P < 0.001). The time to complete FDR was longer in ESRD patients (110 +/- 54 vs. 162 +/- 72 s, P < 0.001). ESRD patients had lower high-density lipoprotein cholesterol and serum albumin (P < 0.01) and higher triglycerides, fibrinogen, plasma homocysteine, vWF (P < 0.01), and PAI-1 (P < 0.05). For ESRD patients, significant negative age- and pressure-independent correlations were established between FDR and CCA diameter, duration of dialysis, and PAI-1. FDR was positively correlated with serum albumin. FDR and time to FDR were negatively correlated with CCA IMT and LV mass. CCA distensibility was positively associated with FDR (P < 0.001) and negatively with time to FDR (P < 0.001). The PAI-1 concentration was positively correlated with CCA IMT (P < 0.01) and negatively with CCA distensibility (P < 0.001). CONCLUSIONS: Our data provide the first evidence that cardiac and arterial remodeling in ESRD patients are inversely related to forearm reactive hyperemia. The diminished hyperemic response is due to the shorter duration of hyperemia and is associated with higher concentrations of serum markers of endothelial activation, suggesting that, in ESRD patients, endothelial dysfunction may be a factor influencing cardiovascular changes. (+info)
Pulsatile flow enhances endothelium-derived nitric oxide release in the peripheral vasculature.
(46/956)
The effects of pulsatility in blood flow on endothelium-derived nitric oxide (EDNO) release in the peripheral vasculature were investigated. The basal and flow-stimulated EDNO release were compared between pulsatile and nonpulsatile systemic flows before and after the administration of NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Peripheral vascular resistance (PVR) was significantly lower in pulsatile flow than in nonpulsatile flow, but this difference disappeared after L-NMMA. The percent increase in PVR by L-NMMA was significantly larger in pulsatile flow. In reactive hyperemia in the hindlimb, the peak flow did not differ; however, both the repayment flow and the duration were significantly larger in pulsatile flow. Percent changes of these parameters by L-NMMA were significantly larger in pulsatile flow. These data indicated that pulsatility significantly enhances the basal and flow-stimulated EDNO release in the peripheral vasculature under in vivo conditions. We also studied the involvement of the Ca(2+)-dependent and Ca(2+)-independent pathways in flow-induced vasodilation using calmodulin inhibitor calmidazolium and tyrosine kinase inhibitor erbstatin A. PVR was significantly elevated by erbstatin A but not by calmidazolium, suggesting that flow-induced vasodilation was largely caused by tyrosine kinase inhibitor-sensitive activation of NO synthase. (+info)
Long-term right ventricular volume overload increases myocardial fluorodeoxyglucose uptake in the interventricular septum in patients with atrial septal defect.
(47/956)
BACKGROUND: Several studies have shown that long-term right ventricular (RV) overload in animal models alters myocardial energy substrate metabolism. However, whether long-term RV volume overload alters this metabolism in the human is unclear. METHODS AND RESULTS: We performed positron emission tomography with [(18)F]fluorodeoxyglucose (FDG) and single-photon emission tomography (SPECT) with [(201)Tl]TlCl (Tl) and [(123)I]15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in 11 patients with atrial septal defect (ASD) and 11 control subjects. In the FDG study, we calculated myocardial metabolic rate of glucose (MMR) in interventricular septum (IVS) and left ventricular (LV) free wall. MMR was significantly increased in IVS compared with LV free wall in the ASD patients (420+/-35 versus 333+/-32 mol x kg(-1) x min(-1); P<0.05) but not in the control group (347+/-27 versus 357+/-25 mol x kg(-1) x min(-1)). In both ASD and control groups, SPECT count was not significantly different between IVS and LV free wall in Tl (ASD, 160+/-11 versus 177+/-12; control, 141+/-12 versus 157+/-14 counts per 15 minutes) and BMIPP studies (ASD, 203+/-14 versus 212+/-18; control, 162+/-16 versus 176+/-16 counts per 15 minutes). MMR in the IVS/LV free wall ratio in the ASD group significantly correlated with indices related to RV volume overload. CONCLUSIONS: Given the assumption that long-term RV volume overload did not affect the lumped constant, the present study suggests that, unlike myocardial perfusion or fatty acid analogue uptake, myocardial glucose utilization in IVS relative to LV free wall is increased in relation to long-term RV volume overload in patients with ASD. (+info)
Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison with intracoronary Doppler method.
(48/956)
To evaluate the feasibility and usefulness of transthoracic Doppler echocardiography (TTDE) as a non-invasive method in recording distal anterior descending (LAD) coronary flow velocity, we compared coronary flow reserve (CFR) measured by TTDE with measurements by intracoronary Doppler wire (ICDW). Twenty-one patients without LAD stenosis were studied. ICDW performed at baseline and after intracoronary injection of 18 microg adenosine. TTDE was performed at baseline and after intravenous adenosine (140 microg/kgmin for 2 min). Adequate Doppler recordings of coronary flow velocities during systole were obtained in 14 of 21 study patients (67%) and during diastole in 17 (81%) patients. Baseline and hyperemic peak diastolic flow velocities measured by TTDE were significantly smaller than those obtained by ICDW (p<0.05). However, diminishing trends of diastolic and systolic velocity ratio after hyperemia were similarly observed in both methods. CFR obtained by TTDE (3.0+/-0.5), was higher than the value calculated by ICDW (2.5+/-0.4). There were significant correlations between the values obtained by the two methods (r=0.72, p<0.01). It is concluded that TTDE is a feasible method in measuring coronary flow velocity and appears to be a promising non-invasive method in evaluating CFR. (+info)