Caregiver psychological characteristics predict discontinuation of care for disabled elderly at home.

OBJECTIVE: This study sought to determine the predictors of discontinuation of care for the disabled elderly at home using multivariate regression analysis. METHODS: In January to February 2005, using a self-administered questionnaire, data were collected from 193 caregivers of frail elderly listed on a roster for utilization of day service or short stay service from two Home Visit Nursing Care Stations. Family caregivers were defined as co-resident family members who provided a minimum of 1 h of daily care for at least 3 months. Multiple stepwise logistic regression analysis was performed to detect predictors of a discontinuation for the disabled elderly at home. RESULTS: The mean age of caregivers was around 59.0 years, accounting for about 80% of the women among caregivers. Of those caregivers, the proportion of desire to institutionalization (high DI) (56.8%) was higher than that of desire to care at home (low DI) (43.2%). Among the following three factors selected by multivariate stepwise logistic regression analysis, the strength of the relationship was stronger in frequent mood swings and irritability as carerecipient characteristic (adjusted OR = 5.93; 95% CI, 2.09-16.8) than in no advanced or skilled care (adjusted OR = 3.13; 95% CI, 1.41-7.14) and a high caregiver burden (adjusted OR = 1.12; 95% CI, 1.03-1.23) as caregiver's one. CONCLUSIONS: Our results suggest that the carerecipients' psychological characteristics may be more strongly related to the decision to continue care for disabled elderly at home than that of the caregivers'.

Role of endogenous nitric oxide in the brain stem on the rapid adaptation of baroreflex.

It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of N(omega)-nitro-L-arginine methyl ester (L-NAME, 8 micromol), N(omega)-nitro-D-arginine methyl ester (D-NAME, 8 micromol), L-arginine (40 micromol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle. L-Arginine reversed the effects of L-NAME. However, D-NAME or L-arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.

Short-term estrogen administration ameliorates dobutamine-induced myocardial ischemia in postmenopausal women with coronary artery disease.

OBJECTIVES: This study was designed to examine whether short-term estrogen administration ameliorates dobutamine-induced myocardial ischemia in postmenopausal women with coronary artery disease (CAD). BACKGROUND: Estrogen replacement therapy in postmenopausal women is associated with a marked reduction in the risk of CAD. Estrogen has been reported to have both short- and long-term effects on the cardiovascular system. However, it remains to be examined whether short-term estrogen administration ameliorates myocardial ischemia caused by increased myocardial oxygen demand in postmenopausal women with CAD. METHODS: Eight postmenopausal women with proved CAD underwent dobutamine stress echocardiography (DSE). DSE was performed three times in a placebo-controlled, double-blind manner: 1) 30 min after intravenous administration of saline solution (placebo) and after 2) a low dose (1.25 mg) and 3) a high dose (10 mg) of conjugated estrogen. The effects of estrogen were compared at the maximal comparable stage of DSE, which was the maximal DSE level that the same patient achieved in all three examinations. RESULTS: Estrogen dose-dependently ameliorated the dobutamine-induced worsening of symptoms (prolonging time to onset of symptoms by 52% [low dose] and 72% [high dose]), electrocardiographic findings (decreasing the magnitude of summed ST segment changes by 36% [low dose] and 76% [high dose]) and left ventricular wall motion (reducing the wall motion score index by 50% [low dose] and 77% [high dose], all p < 0.01 by analysis of variance). There was no significant difference in blood pressure, heart rate or rate-pressure product among the three examinations at the maximal comparable stage of DSE. CONCLUSIONS: Estrogen has short-term anti-ischemic effects on the myocardial ischemia induced by increased myocardial oxygen demand in postmenopausal women with CAD.

Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure.

It is unknown whether basal release of endothelium-derived nitric oxide in the coronary artery is altered in heart failure in humans. The aim of the present study was to evaluate the effect of inhibition of nitric oxide synthesis on basal tone of the conduit and resistance coronary arteries in awake patients. Coronary blood flow velocity (Doppler guide wire) and coronary arterial diameter (quantitative coronary angiography) were measured in 14 patients with heart failure caused by nonischemic left ventricular dysfunction (7 idiopathic dilated cardiomyopathy and 7 valvular insufficiency) and 7 patients with normal ventricular function (controls). Intracoronary N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, at graded doses decreased coronary blood flow in both groups. However, the magnitude of flow reduction was smaller in patients with heart failure than in control patients (P<.0001). The magnitude of coronary blood flow reduction in response to L-NMMA inversely correlated to indexes of left ventricular contractile function (P<.01) but was not affected by the cause of heart failure. Constriction of the large epicardial coronary artery with L-NMMA also tended to be attenuated in patients with heart failure. In summary, vasoconstricting response to L-NMMA was blunted in the coronary resistance artery in heart failure in vivo. These findings suggest that basal release of nitric oxide in the coronary circulation is decreased in patients with heart failure.

Coupled vs. uncoupled pericardial constraint: effects on cardiac chamber interactions.

The effects of pericardial constraint on cardiac chamber interactions were evaluated by mathematical model analyses based on a novel concept of coupled vs. uncoupled pericardial constraint. We hypothesized that the nature of pericardial constraint can be classified as a "coupled" constraint exerted by uniform liquid pressure or an "uncoupled" constraint exerted by regional surface pressure. The numerical solution of the model of atrioventricular interaction produced the characteristic waveforms in venous flows and right atrial/ventricular pressures in classical pericardial diseases. Coupled constraint accounted for the patterns in cardiac tamponade; uncoupled constraint accounted for those in constrictive pericarditis. Analytic solution of the model of ventricular interdependence demonstrated that coupled constraint (tamponade) produced greater gains in ventricular interdependence, increasing the occurrence of pulsus paradoxus, whereas uncoupled constraint (constriction) produced a greater effective right ventricular elastance, increasing the likelihood of Kussmaul's sign. Thus the concept of coupled vs. uncoupled constraint may offer a coherent framework to understand the characteristic steady-state and respiratory-induced hemodynamic events in multiple forms of pericardial diseases.

Extensive use of artificial chordae for repairing diffuse mitral valve prolapse.

A diffuse mitral valve prolapse was successfully repaired in 2 patients using polytetrafluoroethylene sutures as artificial chordae. In a 16-year-old boy with Marfan's syndrome and in a 56-year-old woman, a total of 11 and ten pairs of polytetrafluoroethylene sutures were used, respectively, to repair a severe mitral valve prolapse. We consider mitral valve repair using polytetrafluoroethylene sutures to be the treatment of choice for a diffuse prolapse of the mitral valve involving both the anterior and posterior leaflets.

Transfer function analysis of central arc of aortic baroreceptor reflex in rabbits.

While electrically stimulating the aortic depressor nerve (ADN) pseudorandomly, we recorded renal sympathetic nerve activity (RSNA) and systemic arterial pressure (SAP) in 19 alpha-chloralose-anesthetized rabbits with sinoaortic denervation. From the recorded signals, we determined the transfer functions from ADN stimulation by a pseudorandom binary sequence to RSNA [HCMD.RSNA(f)] and to SAP [HCMD.SAP(f)]. The modulus of HCMD.RSNA(f) was flat over 0.0122-0.8 Hz, whereas the phase lag increased linearly with frequency. Thus the central transduction appeared not to modify the relative amplitude of the signals from the baroreflex afferents but to provide a fixed time delay (approximately 400 ms). In contrast, the modulus of HCMD.SAP(f) decreased precipitously toward high frequencies, and the degree of the phase lag was larger than that of HCMD.RSNA(f). We conclude that 1) the transfer property of the central are does not significantly modify the relative amplitude of the frequency components of the baroreflex afferents but provides a fixed time delay and 2) the frequency independence of the modulus of the transfer property is not preserved when the analysis is extended to SAP.

Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, U-97018.

We examined the pharmacological properties of U-97018, a novel nonpeptide angiotensin II (AII) receptor antagonist, in various in vitro and in vivo studies. U-97018 selectively displaced 125I-AII specific binding in the membrane fraction derived from the rat mesenteric artery and adrenal cortex (AT1 subtype) with IC50 of 1.3 +/- 0.2 and 7.7 +/- 1.3 nM, respectively, without altering the AII binding of the rat adrenal medulla (AT2 subtype). In rat adrenal cortical cells, U-97018 inhibited 1 nM AII-induced aldosterone secretion with an IC50 of 0.48 nM; it shifted concentration-secretion response curve for AII to the right and inhibited the maximal response to AII, yielding a pKB of 9.8. Similarly, U-97018 showed insurmountable antagonism with a pKB of 10.6 against the AII-induced contraction in the isolated rabbit aorta. U-97018 had no direct effect on the activities of renin and angiotensin converting enzyme in vitro. In pithed rats, U-97018 inhibited the AII-induced pressor response with an ED50 of 0.28 mg/kg, i.v. without any partial agonistic activity. In anesthetized rats and dogs, intraduodenal administration of U-97018 at a dose of 1 mg/kg inhibited the AII-induced pressor response by about 60%. In spontaneously hypertensive rats, U-97018 at 10 mg/kg p.o. produced antihypertensive effects which lasted for 24 hr after administration. Thus, U-97018 is an orally active, insurmountable AII receptor antagonist without any agonistic activity.

Bradykinin-induced vasodilation is impaired at the atherosclerotic site but is preserved at the spastic site of human coronary arteries in vivo.

BACKGROUND: Bradykinin causes endothelium-dependent vasodilation of isolated human coronary arteries in vitro. However, the effect of bradykinin on vasomotion of human coronary arteries in vivo has not been studied. The aim of this study was to examine whether bradykinin-induced vasodilation is altered at the atherosclerotic or spastic site of human coronary arteries in vivo. METHODS AND RESULTS: The effect of bradykinin on vasomotion of epicardial coronary arteries was evaluated in 8 patients with normal coronary arteries (control group), 14 patients with organic coronary stenosis (coronary artery disease [CAD] group), and 8 patients with vasospastic angina (VSA group). Changes in the diameter of epicardial coronary artery were assessed by quantitative coronary arteriography. Intracoronary administration of bradykinin at graded doses (60, 200, and 600 ng) dilated epicardial coronary arteries without altering arterial pressure or heart rate in all patients of either group. In the control group, vasomotor responses of the site where acetylcholine caused dilation were compared with the responses of the site where acetylcholine caused constriction. The magnitudes of bradykinin-induced dilation at the site with acetylcholine-induced dilation (mean +/- SD: 6 +/- 6%, 11 +/- 9%, and 15 +/- 9%) were comparable to that (3 +/- 6%, 8 +/- 8%, and 13 +/- 9%) at the site with acetylcholine-induced constriction. In the CAD group, vasomotor responses of the stenotic site (% diameter stenosis, 15% to 50%) and nonstenotic site were examined. The bradykinin-induced dilation at the stenotic site (0 +/- 4%, 3 +/- 8%, and 5 +/- 9%) was significantly less (P < .01) than at the nonstenotic site (3 +/- 4%, 8 +/- 6%, and 16 +/- 11%) and in the control group. Coronary vasodilation with nitrate at the stenotic site (20 +/- 11%) was comparable to that at the nonstenotic site (22 +/- 16%) and in the control group (21 +/- 10%). In the VSA group, vasomotor responses of the site with acetylcholine-induced spasm and the site without spasm were examined. The bradykinin-induced vasodilation at the spastic site (5 +/- 5%, 16 +/- 15%, and 33 +/- 17%) was comparable to that at the nonspastic site (4 +/- 8%, 12 +/- 14%, and 21 +/- 9%). Nitrate-induced dilation was comparable at the spastic site (51 +/- 19%) and the nonspastic site (32 +/- 13%). The ratio of bradykinin-induced vasodilation to nitrate-induced vasodilation at the spastic site was comparable to the control group. CONCLUSIONS: These results suggest that bradykinin causes vasodilation of human epicardial coronary arteries in vivo and that bradykinin-induced endothelium-dependent vasodilation is impaired at the stenotic site but is preserved at the angiographically normal site where endothelium-dependent vasodilation by acetylcholine is impaired and at the spastic site.

A rare case of large ventricular septal defect with minimal pulmonary vascular obstructive changes in a 41-year-old woman.

We describe a case of large ventricular septal defect (VSD) with minimal obstructive changes in the small pulmonary arteries of a 41-year-old woman. Before cardiac catheterization, some laboratory findings led us to consider that surgical closure of the defect would not be possible. However, because hemodynamic examinations showed only mildly elevated pulmonary vascular resistance, we patch-closed the VSD successfully. The histology of lung specimens showed only minimal obstructive changes in the small pulmonary arteries. Considering the size of the VSD and the age at which we hemodynamically evaluated the patient, the mildness of the pulmonary vascular obstructive changes appeared to be atypical in the natural course of a VSD of this size.

Isoproterenol infusion provokes vasovagal response without upright tilt in a patient exhibiting syncopal episodes.

We report a case of a patient with vasovagal syncope, in whom isoproterenol infusion provoked vasovagal response without upright tilting. We subjected the patient, who had had two previous syncopal and several presyncopal episodes, to upright tilting with isoproterenol infusion. Before a control tilt was performed for 10 min (80 degrees), the patient was placed in the supine position for 5 min. The control tilt did not provoke a vasovagal response. With isoproterenol being infused at a dose of 1 mu g/min, the sequence of positioning in the supine position for 5 min and upright tilting for 10 min was repeated. This dose of isoproterenol infusion did not provoke any vasovagal response in the patient, either in the supine or in the upright position. When the dose of isoproterenol infusion was then increased to 2 mu g/min, the heart rate increased to 121/min, but then suddenly dropped to 74/min; systemic arterial pressure simultaneously fell from 148/80 to 108/80 mmHg. The patient complained of palpitation and anxiety, and showed profound cold sweating. The drop in the heart rate and the fall in blood pressure occurred when the patient was in the supine position, indicating that, unlike upright tilting with isoproterenol infusion, venous return was not decreased at the beginning of vasovagal response in this setting. This observation suggests that isoproterenol infusion, even without upright tilting, may provoke the vasovagal response in some patients.

Role of nitric oxide in reactive hyperemia in human forearm vessels.

BACKGROUND: The role of nitric oxide (NO) in reactive hyperemia (RH) is not well known. We investigated whether NO plays a role in RH in human forearm vessels by examining the effects of NG-monomethyl-L-arginine (L-NMMA), a blocker of NO synthesis, on reactive hyperemic flow. METHODS AND RESULTS: Forearm blood flow (FBF) was measured by strain-gauge plethysmography with a venous occlusion technique. The left brachial artery was cannulated for drug infusion and direct measurement of arterial pressure. To produce RH, blood flow to the forearm was prevented by inflation of a cuff on the upper arm to suprasystolic pressure for intervals of 3 and 10 minutes. After the release of arterial occlusion (AO), FBF was measured every 15 seconds for 3 minutes. Resting FBF was 4.3 +/- 0.3 mL.min-1.100 mL-1 before 3 minutes of AO and 4.1 +/- 0.6 mL.min-1.100 mL-1 before 10 minutes of AO. FBF increased to 32.3 +/- 1.9 and 38.2 +/- 3.1 mL.min-1.100 mL-1 immediately after 3 and 10 minutes of AO, respectively, and gradually decayed (n = 13). Intra-arterial infusion of L-NMMA (4 mumol/min for 5 minutes) decreased baseline FBF (P < .01) without changes in arterial pressure. L-NMMA did not affect the peak reactive hyperemic FBF after 3 and 10 minutes of AO. L-NMMA significantly decreased total reactive hyperemic flow (flow debt repayment) by 20% to 30% after 3 and 10 minutes of AO. Simultaneous infusion of L-arginine (a precursor of NO) with L-NMMA reversed the effects of L-NMMA. CONCLUSIONS: Our results suggest that NO plays a minimal role in vasodilation at peak RH but plays a modest yet significant role in maintaining vasodilation after peak vasodilation. Our results also suggest that reactive hyperemia in human forearms is caused largely by mechanisms other than NO.

Dynamic arterial baroreflex in rabbits with heart failure induced by rapid pacing.

Excessive sympathetic nerve activity in heart failure could be attributable to impaired arterial baroreflex function. Employing transfer function analysis, we evaluated the arterial baroreflex in control rabbits (n = 8) and in rabbits with rapid pacing-induced heart failure (n = 10) in a dynamic manner. Rabbits in the heart-failure group showed elevated filling pressures, depressed first derivative of left ventricular pressure, pulmonary congestion, and an increased level of plasma norepinephrine. Varying aortic pressure pseudorandomly and recording responses in renal nerve activity, we calculated the transfer function from aortic pressure to renal nerve activity. The gain of the transfer function was similar between control and heart-failure rabbits over 0.04-0.4 Hz as well as the phase and the coherence, indicating that the dynamic arterial baroreflex was preserved in our rabbit heart-failure model. Vagotomy increased the gain of the arterial baroreflex over 0.04-0.4 Hz in control (P < 0.05) but not in heart-failure rabbits, indicating that vagal afferents, which normally inhibit the dynamic arterial baroreflex, no more did so in heart failure. We conclude that excessive sympathetic nerve activity in heart failure may not be due to impaired dynamic arterial baroreflex, but that this apparently preserved arterial baroreflex in heart failure may be due to impaired cardiopulmonary baroreflex.

Influence of arotinolol hydrochloride on heart rate spectrum in hypertensive subjects.

Influence of arotinolol hydrochloride and atenolol on the balance between the sympathetic and parasympathetic nervous systems was evaluated in 8 hypertensive subjects by spectral analysis of heart rate (HR) and systemic blood pressure (BP). Before and after administration of either arotinolol (n = 7) or atenolol (n = 7) for 2 weeks, BP was continuously and non-invasively monitored by a finger-cuff manometry (Finapres). A time series of instantaneous HR was constructed from the BP signal. A time series of mean BP was also constructed. Spectral analysis was performed by the use of an autoregressive algorithm on these time series (approximately 180 sec). Each spectrum was subdivided into low-(0.05-0.15 Hz, LF) and high-frequency (0.15-0.4 Hz, HF) components, and each component was divided by the sum of the two for normalization. As a measure of the balance between the sympathetic and parasympathetic nervous systems, the ratio of LF to HF (LF/HF) was evaluated. Arotinolol increased fractional HF in the HR spectrum from 0.45 +/- 0.12 to 0.73 +/- 0.08 (p < 0.01) and decreased fractional LF from 0.55 +/- 0.12 to 0.27 +/- 0.08 (p < 0.01); consequently, it decreased LF/HF from 1.4 +/- 0.5 to 0.4 +/- 0.2 (p < 0.01). Atenolol had similar effects on these parameters. Neither of these beta-adrenergic blockades produced a discernible decrease in LF/HF in the BP spectrum. In conclusion, these beta-adrenergic blockades decreased LF/HF in the HR spectrum in hypertensive subjects, which suggests that they improved the balance between the sympathetic and parasympathetic nervous systems.

Role of carotid sinus baroreflex in attenuating systemic arterial pressure variability studied in anesthetized dogs.

Attenuation of systemic arterial pressure (SAP) variability by the carotid sinus baroreflex (CSBR) was quantified in nine anesthetized, vagotomized dogs. SAP amplitude spectrum was compared between open-loop [SAPo(f)] and closed-loop [SAPc(f)] operation of the CSBR. At 0.002 Hz, SAPc amplitude was 3.5 +/- 2.2 (SD) mmHg, and SAPo was 9.6 +/- 3.5 mmHg (P < 0.01). At 0.02 Hz, SAP(c) amplitude was 2.8 +/- 1.2 mmHg, and SAPo was 4.3 +/- 1.2 mmHg (P < 0.05). At higher frequencies, SAPo(f) was indistinguishable from SAPc(f). With the opened CSBR, intracarotid sinus pressure (CSP) was pseudorandomly varied, and the resulting SAP responses were recorded to determine the transfer function from CSP to SAP [HCSP.SAP(f)]. From SAPo(f) and the determined HCSP.SAP(f), we estimated SAP(f) if the CSBR was closed [SAPc,est(f)] and compared it with SAPc(f). These two spectra were similar in each dog over a frequency range of 0.002-0.15 Hz, the differences between SAPo(f) and SAPc(f) being reconcilable with HCSP.SAP(f). Although the anesthetized state and vagotomy may have distorted the transfer characteristics of the CSBR from those in conscious (with the intact vagi) states, the results of the present study indicate that the CSBR attenuated SAP variability mainly in a low-frequency range below 0.02 Hz and that this attenuation was attributable to the transfer properties of the CSBR.

Transfer function analysis from arterial baroreceptor afferent activity to renal nerve activity in rabbits.

In vagotomized and anesthetized rabbits, aortic pressure (AP), aortic depressor nerve activity (ANA), and renal sympathetic nerve activity (RNA) were simultaneously measured while perturbing AP randomly. To quantitatively characterize the role of the arterial baroreflex system in generating RNA, we determined the transfer function (TF) of the central baroreflex arc from ANA to RNA in the frequency domain (0.02-5 Hz). The magnitude of squared coherence was > 0.5, the phase was close to -180 degrees, and the gain of TF was flat over 0.02-0.3 Hz, indicating that changes in RNA were linearly and instantaneously but inversely related to changes in ANA over this frequency range. Above 0.3 Hz, the coherence was low, suggesting that RNA unrelated to ANA existed in the frequency range. In animals without AP perturbations, power spectrum of RNA resided over 0.2-5 Hz with a broad peak at 1 Hz, which may represent central activity. Our results suggest that over 0.02-0.3 Hz the relationship between arterial baroreceptor afferent nerve activity and RNA is linear and instantaneous but above 0.3 Hz it is not linear possibly due to an interaction between central activity and arterial baroreflex.

Antishock effect of U-67,590A, methylprednisolone suleptanate, associated with restoration of lowered vascular reactivity in endotoxemic rats.

We wished to investigate the modulating effects of a glucocorticoid on mortality and sustained hypotension in endotoxemic rats in conjunction with in vitro study of responses of isolated aorta to KCl, norepinephrine (NE), and acetylcholine (ACh). Endotoxemia was induced by intravenous (i.v.) bolus injection of 50 mg/kg Escherichia coli endotoxin in rats, resulting in high mortality. Pretreatment with U-67,590A, methylprednisolone suleptanate, at a dose of 9 mg/kg resulted in 100% survival; the survival rate of saline-treated controls was 21%. Isolated rat aorta that had been treated with endotoxin for 4 h showed decreases in contractile responses to KCl and NE and in relaxing response to ACh. Similar attenuation of contractile responsiveness was observed in endothelium-denuded preparations. Addition of endotoxin to the in vitro tissue bath did not inhibit the responses in a 4-h period. Pretreatment with U-67,590A inhibited the late gradual decrease in blood pressure (BP) but not the early hypotensive response to endotoxin. The responses to KCl or NE of aorta isolated 4 h after the endotoxin injection remained suppressed in U-67,590A-treated rats but were restored in 24 h. These results suggest that endotoxemia impairs the endothelium moderately, but this does not account for either reduced reactivity of vascular smooth muscle to vasoconstrictor agents or the sustained hypotension. The steroid inhibits endotoxemia-induced mortality and sustained hypotension.

Contribution of wall mechanics to the dynamic properties of aortic baroreceptors.

To examine the contribution of wall mechanics to dynamic properties of baroreceptors, we subdivided the transfer function of baroreceptors into two subsystems [aortic pressure to diameter and diameter to aortic depressor nerve activity (ANA)]. In six alpha-chloralose-anesthetized rabbits, we measured pressure, diameter, and ANA while randomly perturbing pressure. We obtained transfer functions (pressure to ANA, diameter to ANA, and pressure to diameter) by taking the ratio of crosspower spectrum to the input power spectrum (0.005-5 Hz). Below 3 Hz, the transfer function from pressure to ANA was nearly identical to that from diameter to ANA, whereas that from pressure to diameter was flat. Using transfer functions we could reproduce adaptation and hysteresis that were quantitatively similar between pressure-ANA transduction and diameter-ANA transduction. The pressure-diameter relationship was almost instantaneous and thus showed no hysteresis. In a second group of rabbits, the ratio of the shift of the hysteresis loop was unchanged by ouabain (40 micrograms/kg iv, n = 7). We conclude that the dynamic properties of baroreceptors may not be related to the wall mechanics or the Na(+)-K(+)-adenosinetriphosphatase activity.

Effects of pentobarbital on inotropic state of isolated canine left ventricle.

Although pentobarbital has been found to depress myocardial function, the magnitude of its direct effects on ventricular contraction at anesthetic concentrations has not been well quantified. The direct effects of pentobarbital on left ventricular function were measured by employing an isolated canine heart preparation with a blood oxygenator. Seven hearts were perfused with blood, dextran, and perfluorochemical artificial blood. Ventricular function was evaluated using the slope of the end-systolic pressure-volume relationship (Ees) and the maximal rate of pressure development (dP/dtmax) in ventricles contracting isovolumically in control, after a low dose (13 micrograms/ml), and after a high dose (48 micrograms/ml) of pentobarbital. These concentrations represent one-half and two times the typical value (25 micrograms/ml) found to produce anesthesia in canines (assessed by tail clamp or blink reflex). The low dose of pentobarbital did not produce clear-cut depression in contractile function. The high dose of pentobarbital produced significant reductions of Ees, and dP/dtmax: Ees decreased 29%, from a control of 4.30 +/- 0.84 to 3.05 +/- 0.49 mmHg/ml and dP/dtmax decreased 24%, from a control of 909 +/- 148 to 695 +/- 173 mmHg/s. Thus, the threshold for the direct depressant effect of pentobarbital on ventricular function falls within the range of half to double the typically-reported anesthetic concentrations.

Recovery of endothelium-dependent responses by reseeding endothelial cells in culture onto the denuded coronary artery.

Endothelium-denuded coronary artery was reseeded with the endothelial cells in culture, and the endothelium-dependent responses were compared with those in arteries with or without native endothelium. A23187 produced a relaxation in the arterial preparations reseeded with cultured endothelial cells in the cell suspension of 10(5) cells/ml for 17 to 19 hr, whereas no relaxation was observed in the denuded artery. Relaxing response to Ca++ ionophore A23187 was dependent on the number of endothelial cells reseeded. The A23187-induced relaxation in the cell-reseeded artery was inhibited markedly by pretreatment with 3 x 10(-4) M NG-monomethyl-L-arginine or 5 x 10(-5) M methylene blue, but not 10(-4) M aspirin. NG-monomethyl-L-arginine (3 x 10(-4) M) and methylene blue (5 x 10(-5) M) produced a contraction in the cell-reseeded artery. Contraction evoked by bradykinin in the denuded arteries was attenuated by reseeding endothelial cells. KCl-induced contraction in the endothelium-reseeded artery did not differ from that in the denuded artery. Contractile responses to norepinephrine and serotonin were attenuated by reseeding endothelial cells onto the denuded artery to a small extent. Scanning electron microscopy showed that the luminal surface of endothelium-reseeded arteries was partly covered with endothelial cells. We conclude that when the cultured endothelial cells are reseeded onto a denuded coronary artery, endothelium-derived relaxing factor release occurs, but endothelium-dependent mechanisms are not the same as those for native cells.