Left ventricular wall stress during leg-press exercise performed with a brief Valsalva maneuver

STUDY OBJECTIVES: To assess the effects of leg-press (LP) exercise performed with a brief (2 to 3 s) Valsalva maneuver on left ventricular (LV) systolic function and LV wall stress in five healthy men (mean +/- SD age, 27.6 +/- 2.9 years). METHODS AND MEASUREMENTS: Subjects performed submaximal (80% one repetition maximum [1RM], 337.9 +/- 109.1 kg; 95% 1RM, 400.6 +/- 129.8 kg) and maximal LP exercise (420 +/- 118.6 kg) during which central arterial pressure, intrathoracic pressure, and two-dimensional echocardiographic analysis of LV systolic function and LV wall stress were measured. RESULTS: Compared with baseline, LP exercise resulted in an increase in intrathoracic pressure (baseline, 1.7 +/- 2.9 mm Hg; 80% 1RM, 111.7 +/- 20.2 mm Hg; 95% 1RM, 112.2 +/- 21.1 mm Hg; 100% 1RM, 111.0 +/- 21.3 mm Hg; p < 0.05) and LV end-systolic pressure (baseline, 120.0 +/- 13.2 mm Hg; 80% 1RM, 251.6 +/- 15.3 mm Hg; 95% 1RM, 255.3 +/- 12.2 mm Hg; 100% 1RM, 242.8 +/- 16.5 mm Hg; p < 0.05) with no changes in LV end-systolic transmural pressure (baseline, 118.3 +/- 12.6 mm Hg; 80% 1RM, 140.0 +/- 6.1 mm Hg; 95% 1RM, 143.1 +/- 16.1 mm Hg; 100% 1RM, 131.8 +/- 29.7 mm Hg; p > 0.05), LV end-systolic wall stress (baseline, 91.7 +/- 20.2 kilodyne/cm(2); 80% 1RM, 78.0 +/- 24.4 kilodyne/cm(2); 95% 1RM, 81.4 +/- 25.3 kilodyne/cm(2); 100% 1RM, 85.9 +/- 20.1 kilodyne/cm(2); p > 0.05), or LV fractional area change (baseline, 0.48 +/- 0.03; 80% 1RM, 0.52 +/- 0.11; 95% 1RM, 0.53 +/- 0.06; 100% 1RM, 0.52 +/- 0.05; p > 0.05). CONCLUSION: LP exercise performed with a brief Valsalva maneuver is not associated with an alteration in LV wall stress or LV systolic function in healthy young men.     

Apnea-hypopnea threshold for CO2 in patients with congestive heart failure

To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart failure (CHF), we measured the end-tidal carbon dioxide pressure (PET(CO2)) during spontaneous breathing, the apnea-hypopnea threshold for CO2, and then calculated the difference between these two measurements in 19 stable patients with CHF with (12 patients) or without (7 patients) CSA during non-rapid eye movement sleep. Pressure support ventilation was used to reduce the PET(CO2) and thereby determine the thresholds. In patients with CSA, 1.5-3% CO2 was supplied temporarily to stabilize breathing before determining the thresholds. Unlike patients without CSA whose eupneic PET(CO2) increased during sleep (37.7 +/- 1.4 mm Hg versus 40.2 +/- 1.5 mm Hg, p < 0.01), patients with CSA showed no rise in PET(CO2) from wakefulness to sleep (37.5 +/- 0.9 mm Hg versus 38.2 +/- 1.0 mm Hg, p = 0.2). Patients with CHF and CSA had their eupneic PET(CO2) closer to the threshold PET(CO2) than patients without CSA (DeltaPET(CO2) [eupneic PET(CO2) - threshold PET(CO2)] was 2.8 +/- 0.3 mm Hg versus 5.1 +/- 0.7 mm Hg for apnea, p < 0.01; 1.7 +/- 0.7 versus 4.1 +/- 0.5 mm Hg for hypopnea, p < 0.05). In summary, patients with CHF and CSA neither increase their eupneic PET(CO2) during sleep nor proportionally decrease their apnea-hypopnea threshold. The resultant narrowed DeltaPET(CO2) predisposes the patient to the development of apnea and subsequent breathing instability.     

Structure of cerebral arterioles in mice deficient in expression of the gene for endothelial nitric oxide synthase

We examined effects of pharmacological inhibition of nitric oxide synthase (NOS) and genetic deficiency of the endothelial isoform of NOS (eNOS) on structure and mechanics of cerebral arterioles. We measured pressure, diameter, and cross-sectional area (CSA) of the vessel wall (histologically) in maximally dilated cerebral arterioles in mice that were untreated or treated for 3 months with the NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg per day in drinking water). Treatment with L-NAME increased systemic arterial mean pressure (SAP; 143+/-4 versus 121+/-4 mm Hg, P<0.05) and CSA (437+/-27 versus 310+/-34 microm2, P<0.05). These findings suggest that hypertension induced in mice by NOS inhibition is accompanied by hypertrophy of cerebral arterioles. To determine the role of the eNOS isoform in regulation of cerebral vascular growth, we examined mice with targeted disruption of one (heterozygous) or both (homozygous) genes encoding eNOS. Wild-type littermates served as controls. SAP and CSA were significantly increased in homozygous (SAP, 141+/-5 versus 122+/-3 mm Hg in wild-type mice, P<0.05; CSA, 410+/-18 versus 306+/-15 microm2 in wild-type mice, P<0.05), but not in heterozygous (SAP, 135+/-4 mm Hg; CSA, 316+/-32 microm2) eNOS-deficient mice. Carotid ligation normalized cerebral arteriolar pulse pressure did not prevent increases in CSA in homozygous eNOS-deficient mice. Thus, cerebral arterioles undergo hypertrophy in homozygous eNOS-deficient mice, even in the absence of increases in arteriolar pulse pressure. These findings suggest that eNOS plays a major role in regulation of cerebral vascular growth.     

Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen

STUDY OBJECTIVE: To assess the effects of ibuprofen on blood pressure control in patients being treated with antihypertensive drugs. DESIGN: Randomized, blinded, placebo-controlled, parallel trial of ibuprofen compared with acetaminophen and with placebo in 3-week treatment periods. SETTING: A general internal medicine clinic at a university hospital. PATIENTS: Forty-five patients with essential hypertension controlled by treatment with at least two antihypertensive drugs were enrolled. Of these, 41 completed the study; treatment was discontinued in 3 of the 15 patients in the ibuprofen group due to breakage of the drug capsules, and after randomization in 1 of the 14 patients in the placebo group due to unstable angina. All 15 patients in the acetaminophen group completed the study. INTERVENTIONS: All previous antihypertensive regimens were continued. During the 3-week treatment, ibuprofen, 400 mg, was administered orally every 8 hours; acetaminophen, 1 g, orally every 8 hours; or placebo, 2 capsules, orally every 8 hours. MEASUREMENTS AND MAIN RESULTS: In the ibuprofen group, the mean increase from baseline after 3 weeks of treatment was significant in the average supine diastolic blood pressure (6.4 mm Hg; 95% confidence interval [CI], 1.05 to 11.75; p = 0.0239); supine mean arterial pressure (6.6 mm Hg; 95% CI, 1.25 to 11.95; p = 0.0205); and sitting mean arterial pressure (5.8 mm Hg; 95% CI, 1.57 to 10.04; p = 0.0123). The mean increase in blood pressure variables in the ibuprofen group was significantly different compared with the mean increase in the variables in the placebo group after 3 weeks of treatment: supine systolic blood pressure (7.1 mm Hg compared with -4.5 mm Hg; 95% CI for the difference in means, 2.5 to 20.6; p = 0.0133); supine diastolic pressure (6.4 mm Hg compared with 0.0; 95% CI for difference in means, 0.87 to 12.4; p = 0.0250); supine mean arterial pressure (6.6 mm Hg compared with -1.5; 95% CI for difference in means, 2.0 to 14.2; p = 0.0110); sitting systolic pressure (6.8 mm Hg compared with -3.7; 95% CI for difference in means, 2.0 to 19.0; p = 0.0169); sitting diastolic pressure (5.3 mm Hg compared with -1.1; 95% CI for difference in means, 0.76 to 12.1; p = 0.0273); and sitting mean arterial pressure (5.8 mm Hg compared with -2.0; 95% CI for difference in means, 1.5 to 14.1; p = 0.0169).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of abruptly increased intrathoracic pressure on coronary blood flow velocity in patients

To assess the effects of abruptly increased intrathoracic pressure on coronary blood flow, arterial pressure, heart rate, and intracoronary Doppler blood flow velocity were measured continuously during cough(s) and again during the four phases of the Valsalva maneuver in 14 patients. Coughing significantly increased the systolic pressure (137 +/- 25 to 176 +/- 30 mm Hg), diastolic pressure (72 +/- 10 to 84 +/- 18 mm Hg), and arterial pulse pressure (65 +/- 27 to 92 +/- 35 mm Hg), with no change in heart rate. The mean coronary flow velocity decreased (17 +/- 10 to 14 +/- 12 cm/sec, p less than 0.03). During the Valsalva maneuver, despite marked reduction in the mean arterial pressure during phase III (96 +/- 12 to 68 +/- 14 mm Hg, p less than 0.05), the reduction of coronary blood flow velocity did not achieve statistical significance. These data demonstrate that neither type of abrupt physiologic increase in intrathoracic pressure enhances coronary blood flow. Coughing does not improve coronary perfusion pressures or flow velocity, despite marked increases in arterial diastolic pressure. The Valsalva maneuver, for the most part, does not significantly alter coronary blood flow velocity.     

Spectrum of hemodynamic changes in cardiac tamponade

To investigate the pathophysiology of cardiac tamponade, the hemodynamics of 77 consecutive patients with greater than 150 ml of pericardial effusion were studied. Patients were classified into 3 groups based on the equilibration of intrapericardial with right atrial and pulmonary arterial wedge pressures (mm Hg): group I (n = 16), intrapericardial pressure was less than right atrial and pulmonary arterial wedge pressures; group II (n = 13), intrapericardial pressure was equilibrated with right atrial but not pulmonary arterial wedge pressures; group III (n = 48), intrapericardial pressure was equilibrated with right atrial and pulmonary arterial wedge pressures. Pericardiocentesis produced the following changes: group I--significant (p less than 0.03) decreases in intrapericardial pressure (7 +/- 2 mm Hg), right atrial pressure (3 +/- 2 mm Hg), pulmonary arterial wedge pressure (2 +/- 2 mm Hg), and the inspiratory decrease in arterial systolic pressure (3 +/- 4 mm Hg) but no significant change in cardiac output; group II--significant (p less than 0.02) decreases in intrapericardial pressure (11 +/- 5 mm Hg), right atrial pressure (6 +/- 4 mm Hg), pulmonary arterial wedge pressure (4 +/- 5 mm Hg), and inspiratory decrease in arterial systolic pressure (8 +/- 7 mm Hg), and increase in cardiac output (1.1 +/- 1.2 liters/min); group III--significant (p less than 0.001) decreases in intrapericardial pressure (16 +/- 7 mm Hg), right atrial pressure (9 +/- 4 mm Hg), pulmonary arterial wedge pressure (8 +/- 5 mm Hg), inspiratory decrease in arterial systolic pressure (17 +/- 11 mm Hg), and increase in cardiac output (2.8 +/- 1.5 liters/min). The changes after pericardiocentesis in all parameters were significantly (p less than 0.05) greater in group III than in groups I or II except for the change in right atrial pressure, which was not significantly different in groups II versus III. The changes after pericardiocentesis indicate pericardial effusion caused the greatest abnormalities in group III but also caused significant abnormalities of pressure and flow in group II and of pressure alone in group I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on cerebral arterioles in rats

We examined the effects of an angiotensin-converting enzyme inhibitor, perindopril, and a beta-blocker, propranolol, on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). The structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were untreated or treated for 3 months with a high (2 mg/kg per day) or a low (0.3 mg/kg per day) dose of perindopril or propranolol (250 mg/kg per day) alone or in combination with the low dose of perindopril. We measured pressure, external diameter, and cross-sectional area of the vessel wall (CSA) in maximally dilated (with EDTA) cerebral arterioles. Treatment of SHRSP with the high dose of perindopril or the combination of propranolol and the low dose of perindopril normalized cerebral arteriolar mean pressure (50+/-1 [mean+/-SEM] and 43+/-2 mm Hg vs 50+/-1 mm Hg in WKY and 94+/-3 mm Hg in untreated SHRSP; P<0.05), pulse pressure (15+/-1 and 16+/-1 mm Hg vs 13+/-1 mm Hg in WKY and 35+/-1 mm Hg in untreated SHRSP; P<0.05), and CSA (1103+/-53 and 1099+/-51 microm2, respectively, vs 1057+/-49 microm2 in WKY and 1281+/-62 microm2 in untreated SHRSP; P<0.05). In contrast, treatment of SHRSP with the low dose of perindopril or propranolol alone did not normalize arteriolar pulse pressure (24+/-1 and 21+/-1 mm Hg) and failed to prevent increases in CSA (1282+/-77 and 1267+/-94 microm2). Treatment with either dose of perindopril or the combination of propranolol and perindopril significantly increased external diameter in cerebral arterioles of SHRSP (99+/-3, 103+/-2, and 98+/-3 microm vs 87+/-2 microm in untreated SHRSP; P<0.05), whereas propranolol alone did not (94+/-3 microm; P>0.05). These findings suggest that effects of angiotensin-converting enzyme inhibitors on cerebral arteriolar hypertrophy in SHRSP may depend primarily on their effects on arterial pressure, particularly pulse pressure, whereas their effects on cerebral arteriolar remodeling (defined as a reduction in external diameter) may be pressure independent.     

Decreased intraocular pressure in dogs with one-kidney, one wrapped hypertension

We examined the relationship of intraocular pressure and the development of one-kidney, one wrapped (perinephritic) hypertension in the dog. Conscious femoral arterial pressure (direct arterial puncture) and intraocular pressure (Schiotz tonometer) were measured weekly before and after the surgical induction of hypertension in 11 healthy male mongrel dogs and before and after unilateral nephrectomy in 15 normotensive control dogs. Preoperative mean arterial pressure (102 +/- 5 vs 99 +/- 8 [SD] mm Hg, hypertensive vs control dogs) and intraocular pressure (18.1 +/- 2.5 vs 17.7 +/- 2.1 mm Hg, hypertensive vs control dogs) were similar in both groups. In normotensive control dogs, mean arterial pressure and intraocular pressure averaged over the postoperative period (4-8 weeks) did not differ significantly from preoperative values. In contrast, during the same period arterial pressure significantly increased and intraocular pressure significantly decreased in hypertensive dogs (arterial pressure, 163 +/- 8 mm Hg; intraocular pressure, 11.9 +/- 4.0 mm Hg; p less than 0.001 for both values compared with corresponding values in control dogs). Intraocular pressure was inversely related to arterial pressure in hypertensive dogs (r = 0.56, p less than 0.01). These observations indicate that intraocular pressure decreases with the development of canine one-kidney, one wrapped hypertension. The mechanism of this decrease may be related to abnormalities in Na+,K+-adenosine triphosphatase activity found in this form of hypertension.     

Coronary microvascular resistance in hypertensive cats.

Chronic systemic hypertension has been shown to alter the distribution of vascular resistance in many microvascular beds. The purposes of this study were to assess the effects of chronic systemic hypertension on the pressure distribution in the coronary microcirculation and to determine the microvascular site where coronary vascular resistance is increased. Cats were made hypertensive using a one-kidney, one-wrap model (Page model). A servonulling system was used to directly measure pressures in the epimyocardial microvessels of the beating left ventricle in normotensive and hypertensive cats. In chronically hypertensive cats, mean arterial pressure was 153 +/- 5 mm Hg compared with 98 +/- 3 mm Hg in normotensive cats (p less than 0.05). Left ventricular mass was increased approximately 34% in hypertensive cats (9.4 +/- 0.3 versus 7.0 +/- 0.3 g, p less than 0.05). Myocardial perfusion measured using radiolabeled microspheres was not different between hypertensive and normal cats. Coronary vascular resistance of the left ventricle was increased in hypertensive cats (0.90 +/- 0.08 versus 0.66 +/- 0.05 mm Hg x min x 100 g/ml, p less than 0.05). Microvascular pressures were measured in three groups of microvessels: small, less than 200 microns; medium, 200-300 microns; and large, greater than or equal to 300 microns. Mean microvascular pressures of large, medium, and small arterial microvessels in hypertensive cats were 144 +/- 8, 127 +/- 6, and 115 +/- 7 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of direct injection of cyclosporine on the arterial vessels of the isolated hind limb in the dog.

Cyclosporine's toxic side effects are widely recognized as a cause of major morbidity. Peripheral vasoconstriction has been suggested as the pathophysiological mechanism for hypertension and renal failure caused by cyclosporine. To study vascular effects on peripheral arterial circulation, cyclosporine was injected into isolated hind limbs perfused at constant flow in the dog. Pure powder cyclosporine was dissolved in a 10% fat emulsion and infused directly into the arterial inflow of the perfused hind limb (n = 7) at a concentration of 5 mg/kg body weight. Reactivity of the vascular bed was first shown by an average decrease of 72 +/- 4 mmHg (95% confidence interval 63 to 81, P less than 0.01) in hind limb perfusion pressure after infusion of 5 mg nitroglycerin. Infusion of fat emulsion did not cause any significant changes. The infusion of cyclosporine caused an average increase of 29 +/- 5 mmHg (95% confidence interval 17 to 41, P less than 0.01) in hind limb perfusion pressure after 4 mins' infusion. After cyclosporine infusion, the vascular bed still responded to nitroglycerin by an average decrease of 56 +/- 5 mmHg (95% confidence interval 42 to 69, P less than 0.01) in perfusion pressure. Blockade of alpha-receptors with phentolamine in five dogs and ipsilateral lumbar sympathectomy in four prevented the increase in perfusion pressure following cyclosporine injection. In conclusion, cyclosporine injected at high doses causes a small vasoconstriction of the peripheral arterial circulation in the hind limb through stimulation of alpha-adrenergic receptors mediated by the sympathetic nervous system. Since the response is completely abolished by sympathectomy, it is probably caused by reflex activation. A direct effect of cyclosporine on the arterial vessel walls of the limb can therefore be excluded.     

Coronary pressure-flow relations in hypertensive left ventricular hypertrophy. Comparison of intact autoregulation with physiological and pharmacological vasodilation in the dog

Coronary pressure-flow relations during autoregulated and vasodilated flow states were compared between eight dogs with renovascular hypertension and left ventricular hypertrophy and 12 normal dogs. Each relation was constructed from serial steady-state measurements of end-diastolic coronary pressure and flow during perfusion of the circumflex artery by an extracorporeal circuit at controlled diastolic pressures of 20-200 mm Hg. Autoregulated pressure-flow relations were compared at three levels of myocardial oxygen demand: resting, high (dobutamine 10 micrograms/kg/min), and low (propranolol 2.5 micrograms/kg/min). Autoregulatory capacity was assessed by calculation of closed-loop flow gain. At each level of myocardial oxygen demand, the lower limit of autoregulation occurred at higher perfusion pressures in the hypertrophy group (rest 65 +/- 3, high 92 +/- 4, low 66 +/- 4 mm Hg) than in the normal group (rest 53 +/- 2, p less than 0.05; high 75 +/- 5, p less than 0.05; low 51 +/- 3 mm Hg) (p less than 0.05). Maximum autoregulatory gain was similar in the normal and hypertrophy groups during resting and low myocardial oxygen demand but was reduced in the hypertrophy group during dobutamine studies. When coronary flow decreased below the lower limit of autoregulation, systolic shortening was reduced in both normal and hypertrophy groups. However, as the autoregulatory limits were at higher pressures in the hypertrophy group, shortening in this group deteriorated at perfusion pressures that did not affect the normal heart. Coronary pressure-flow relations during physiological (peak hyperemia after 15-second flow occlusion) and pharmacologica (intracoronary adenosine 400 micrograms/min) vasodilation was curvilinear and fitted by quadratic regression. During hyperemic vasodilation, maximal conductance per unit mass of myocardium was less in the hypertrophy group over a wide range of perfusion pressures. At a diastolic perfusion pressure of 80 mm Hg, maximum conductance was 4.6 +/- 0.5 ml/min/100 g/mm Hg in the normal group and 3.4 +/- 0.4 ml/min/100 g/mm Hg (p less than 0.05) in the hypertrophy group. Intracoronary adenosine elicited further vasodilation in both groups, but maximum conductance remained less in the hypertrophy group (8.5 +/- 1.7 ml/min/100 g/mm Hg at a perfusion pressure of 80 mm Hg) than in the normal group (13.5 +/- 2.0 ml/min/100 g/mm Hg) (p less than 0.05). Maximal coronary flow reserve is reduced in left ventricular hypertrophy, with a consequent shift of the lower limit of autoregulation to higher perfusion pressures. Thus, as coronary perfusion pressure is decreased, coronary flow and myocardial shortening become impaired at higher     

Minimal increases in pulmonary wedge pressure associated with improved PaO2s in dogs.

To determine the relationship between minimal increases in pulmonary wedge pressure (PWP), arterial PO2s, single breath diffusing capacity (DLCO), and lung perfusion pattern (as determined by semiupright lung scans), we elevated PWP by 61.8+/-4.1% from baseline values of 5.5+/-0.4 mm Hg. At the end of 30 min PaO2 increased by 13.2+/-1.4% (p less than 0.001) from baseline values of 81.7+/-3.1 mm Hg; DLCO decreased by 15.5+/-1.2% (p less than 0.01) to 0.98+/-0.10 ml/min/mm Hg/kg. Lung perfusion changes in the right lung apical zone increased by 28.0+/-4.2% (p less than 0.001) and decreased in the basal zone by 6.2+/-0.8% (NS). In the left lung the apical perfusion increased by 14.9+/-1.1% (p less than 0.01) and basal perfusion decreased by 8.6/+-1.4% (NS). We conclude that minimal elevation of PWP in dogs leads to improvement in PaO2s through alterations in the lungs perfusion pattern.     

Evidence for a renomedullary vasodepressor system in rabbits and dogs

Renal perfusion was increased in anesthetized rabbits and dogs by using an extracorporeal circuit. When left kidney perfusion pressure was raised in rabbits (145-240 mm Hg), arterial pressure fell by 1.34 +/- 0.20 mm Hg/min. Pretreatment of the rabbits with 2-bromoethylamine hydrobromide, which destroyed the renal medulla, abolished the fall in arterial pressure (-0.08 +/- 0.08 mm Hg/min) in response to increased renal perfusion pressure. In dogs (with blockade of autonomic ganglia by pentolinium, converting enzyme inhibition [captopril/enalaprilat], and surgical renal denervation), increasing renal perfusion pressure to 170-220 mm Hg resulted in a fall in arterial pressure by 0.32 +/- 0.03 mm Hg/min (or by 28.9 +/- 3.1 mm Hg over a 90-minute period). Mean arterial pressure did not change significantly in identically prepared dogs not subjected to increased renal perfusion pressure, whereas pretreatment of dogs with bromoethylamine abolished the hypotensive response to increased renal perfusion pressure. Thus, the hypotensive response to increased renal perfusion was dependent on the presence of an intact renal medulla, but hypotension still occurred in the presence of converting enzyme inhibition, autonomic ganglion blockade, and renal denervation. The results provide in vivo evidence in two species that a vasodepressor factor from the renal medulla is released in response to increased renal perfusion.     

Chemical sympathectomy alters the development of hypertension in miniature swine

To determine if the neurotoxin 6-hydroxydopamine could be used to chemically sympathectomize neonatal miniature swine, eight newborn swine were treated with 6-hydroxydopamine beginning on the first day after birth and continuing at regular intervals for the next 6 months. Six littermates served as controls and received vehicle injections. A significant reduction in the pressor response to intravenous tyramine (95%) and in the tissue norepinephrine content of the kidneys, left ventricle, and gastrocnemius muscle (more than 93%) provided evidence for an effective long-term sympathectomy in the 6-hydroxydopamine-treated animals. In addition, the blood pressure response of these young, chemically sympathectomized swine to chronic deoxycorticosterone acetate treatment was evaluated. Mean arterial pressure before deoxycorticosterone was similar in the 6-hydroxydopamine-treated (116 +/- 2 mm Hg) and control (125 +/- 5 mm Hg) groups. One week after deoxycorticosterone, mean arterial pressure had risen significantly by 20-22 mm Hg in both groups. Blood pressure continued to increase in the control group, reaching a value of 163 +/- 6 mm Hg by the third week after treatment. In contrast, mean arterial pressure in the 6-hydroxydopamine group did not increase further during weeks 2 and 3 after deoxycorticosterone. In conclusion, chronic treatment of neonatal swine with 6-hydroxydopamine produced an animal model with an effective, general, peripheral sympathectomy. The significant attenuation of the hypertensive response in these sympathectomized animals lends further support to the hypothesis that an intact sympathetic nervous system is necessary for the full expression of deoxycorticosterone hypertension in miniature swine.     

Renal hemodynamic effects of calcium antagonists in rats with reduced renal mass

The intrarenal hemodynamic effects of antihypertensive agents vary considerably, and these microcirculatory effects may contribute to long-term structural sequelae in the setting of chronic renal disease. To investigate the consequences of blood pressure reduction with calcium antagonists, 5/6 nephrectomized Munich-Wistar rats underwent baseline determinations of mean arterial pressure, whole kidney function, and single nephron glomerular filtration rate, after which intravenous infusions of verapamil or diltiazem were given in doses that acutely normalized blood pressure; control rats received saline vehicle. During the baseline period, all rats exhibited comparably elevated values for mean arterial pressure and single nephron glomerular filtration rate. During the experimental infusion, control rats exhibited continued single nephron hyperfiltration (84 +/- 8 nl/min) as a result of elevations in both glomerular capillary plasma flow rate (330 +/- 36 nl/min) and glomerular capillary hydraulic pressure (68 +/- 3 mm Hg), whereas the glomerular capillary ultrafiltration coefficient was low [0.050 +/- 0.009 nl/(sec.mm Hg)]. Both verapamil (148 +/- 6 to 103 +/- 3 mm Hg, p less than 0.05) and diltiazem (154 +/- 6 to 102 +/- 2 mm Hg, p less than 0.05) normalized arterial pressure, which did not change in control rats (150 +/- 7 to 142 +/- 8 mm Hg). Single nephron hyperfiltration and hyperperfusion were comparable among groups during the experimental period; compared with baseline values, diltiazem (97 +/- 8 to 71 +/- 7 nl/min, p less than 0.05) but not verapamil (90 +/- 7 to 83 +/- 6 nl/min, p = NS) modestly lowered the single nephron glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral oxygenation during exercise in patients with terminal lung disease

STUDY OBJECTIVES: In patients with terminal lung disease who were exercising, we assessed whether improved arterial O2 saturation with an increased fraction of inspired oxygen (FIO2) affects cerebral oxygenation. DESIGN: Randomized, crossover. PATIENTS AND METHODS: The cerebral changes in oxyhemoglobin (DeltaHbO2) and changes in deoxyhemoglobin (DeltaHb) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery (MCA) mean velocity (V(mean)) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease (New York Heart Association class III-IV). Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials. RESULTS: Peak exercise intensity (mean [+/- SE], 26 +/- 4 W) reduced the arterial O2 pressure (at rest, 64 +/- 3 mm Hg; during exercise, 56 +/- 3 mm Hg) and the arterial oxygen saturation (SaO2) [at rest, 92 +/- 2%; 87 +/- 2%; p < 0.05], while the arterial CO2 pressure was not significantly affected. The MCA V(mean) increased from 49 +/- 5 to 63 +/- 7 cm/s (p < 0.05) as did the DeltaHb, while the DeltaHbO2 remained unaffected by exercise. With an elevated FIO2, the SaO2 level (at rest, 95.8 +/- 0.7%; during exercise, 96.0 +/- 1.0%) and arterial O2 pressure (at rest, 102 +/- 11 mm Hg; during exercise, 100 +/- 8 mm Hg) were not significantly affected by exercise, and the levels of blood oxygenation remained higher than the values established at normoxia (p < 0.05). The MCA V(mean) increased to a level similar to that achieved during control exercise (ie, to 70 +/- 11 cm/s). In contrast to control exercise, DeltaHb decreased while DeltaHbO2 increased during exercise with 35% O2 (p < 0.05). CONCLUSION: An O2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O2 saturation during exercise. An exercise-induced increase in cerebral perfusion was not affected by hyperoxia, whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation. The clinical implication of the study is that during physical activity patients with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation.     

Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher

BACKGROUND: The prognostic role of echocardiographic right ventricular (RV) dysfunction for predicting mortality in patients with acute pulmonary embolism and a preserved systemic arterial pressure remains controversial. METHODS: We evaluated 1035 patients with pulmonary embolism from the International Cooperative Pulmonary Embolism Registry who (1) presented with systolic systemic arterial pressure of 90 mm Hg or higher and (2) who underwent echocardiography within 24 hours of a diagnosis of pulmonary embolism, showing presence (n = 405) or absence (n = 630) of RV hypokinesis. The main outcome measure was the cumulative survival rate through 30 days in patients with and without RV hypokinesis. RESULTS: In patients with RV hypokinesis, the initial systolic systemic pressure was lower (125 +/- 22 mm Hg vs 131 +/- 22 mm Hg; P<.001), and the initial heart rate was higher (104 +/- 21 beats per minute vs 99 +/- 22 beats per minute; P<.001) than in patients without RV hypokinesis. Cancer was less often present (14.1% vs 22.5%, P = .001). The 30-day survival rates in patients with and without RV hypokinesis were 83.7% (95% confidence interval [CI], 79.3%-87.0%) and 90.6% (95% CI, 88.0%-92.6%), respectively (log-rank P value <.001). The univariate hazard ratio of RV hypokinesis for predicting 30-day mortality was 2.11 (95% CI, 1.41-3.16; P<.001). Right ventricular hypokinesis remained an independent predictor of 30-day mortality (hazard ratio, 1.94; 95% CI, 1.23-3.06) after adjusting for univariately significant predictors, including cancer, congestive heart failure, chronic lung disease, age older than 70 years, systolic arterial pressure of 100 mm Hg or lower, administration of thrombolytic therapy, and heart rate greater than 100 beats per minutes. CONCLUSION: Among patients with pulmonary embolism who present with a systolic arterial pressure greater than or equal to 90 mm Hg, echocardiographic RV hypokinesis is an independent predictor of early death.     

L-arginine attenuates hypertension in pregnant rats with reduced uterine perfusion pressure

A chronic reduction in uterine perfusion pressure in the pregnant rat is associated with significant elevations in mean arterial pressure, proteinuria, and reductions in kidney function as is chronic nitric oxide blockade, suggesting that nitric oxide deficiency may contribute to the clinical manifestations of preeclampsia. The purpose of this study was to determine whether supplementation with L-arginine, the precursor for nitric oxide, attenuates the hypertension produced in response to a chronic reduction in uterine perfusion pressure in the pregnant rat. Reduced uterine perfusion was initiated at day 14 of gestation with arterial pressure determined at day 19 of gestation in conscious, chronically instrumented rats. Arterial pressure was significantly elevated in pregnant rats with chronic reductions in uterine perfusion as compared with pregnant control rats (132+/-2 versus 109+/-2 mm Hg, P<0.01, respectively). Treatment with L-arginine (2%) in the drinking water was initiated at day 10 of gestation. l-arginine supplementation resulted in a significant decrease in arterial pressure in both pregnant rats with reduced uterine perfusion pressure (113+/-2 mm Hg treated, P<0.01 versus untreated pregnant with reduced uterine perfusion pressure) and pregnant control (97+/-3 mm Hg treated, P<0.01 versus untreated pregnant) rats. However, supplementation with L-arginine decreased blood pressure by 19 mm Hg in pregnant with reduced uterine perfusion pressure (untreated versus treated) as compared with 12 mm Hg in pregnant (untreated versus treated) rats. Thus, these results suggest that l-arginine supplementation may be beneficial in attenuating the hypertension in preeclampsia.     

Rapid baroreceptor resetting in chronic hypertension. Implications for normalization of arterial pressure

The purpose of this study was to examine the ability of baroreceptors of renal hypertensive rabbits to reset rapidly during acute changes in arterial pressure. The carotid sinus (CS) was vascularly isolated and baroreceptor activity was recorded during slow ramp increases in CS pressure in hypertensive (one-kidney, one wrap; 127 +/- 3 mm Hg) and normotensive (one-kidney, no wrap; 85 +/- 3 mm Hg) rabbits anesthetized with chloralose. Control measurements were made after holding pressure for 10-15 minutes at the level of arterial pressure recorded before each experiment. Baroreceptor threshold pressure (Pth) was higher in hypertensives (78 +/- 4 mm Hg) compared with normotensives (55 +/- 3 mm Hg, p less than 0.05), and nerve activity was less in hypertensives over a wide range of pressure. CS distensibility (sonomicrometers) was not significantly different in the two groups. After increasing holding pressure from control by 30 and 60 mm Hg for 10-15 minutes, the extent of baroreceptor resetting (delta Pth/delta holding pressure x 100%) in normotensives was 39 +/- 6% and 33 +/- 2%, respectively, but only 14 +/- 5% and 9 +/- 3% in hypertensives (p less than 0.05). After decreasing holding pressure by 30 and 60 mm Hg, resetting was similar in normotensives (32 +/- 6% and 28 +/- 3%) and hypertensives (34 +/- 3% and 30 +/- 4%). In hypertensive rabbits, acute (10-15 minutes) exposure of baroreceptors to normotension (71 +/- 4 mm Hg) decreased Pth to 62 +/- 4 mm Hg and increased nerve activity to levels not significantly different from those of normotensive animals without altering CS distensibility.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats.

BACKGROUND/AIMS: Increased intrahepatic vascular tone can be pharmacologically manipulated in isolated cirrhotic livers. Intrahepatic endothelial dysfunction may lead to a decreased production of the potent endogenous vasodilator nitric oxide in cirrhotic livers. The aims of the study were to determine whether portal pressure can be lowered in vivo by injecting nitric oxide donors glyceryl trinitrate or nitroprusside directly in the portal vein and whether this is related to a decrease in intrahepatic resistance. METHODS: In anaesthetised CCl4 cirrhotic rats, intraportal doses of glyceryl trinitrate 0.5, 1 or 5 microg/kg/ min or nitroprusside 1, 5 or 10 microg/kg/min did not decrease portal pressure but only arterial pressure. Systemic and splanchnic haemodynamics were measured before and during 15 min intraportal infusion of glyceryl trinitrate 10 microg/kg/min or nitroprusside 20 microg/kg/min. RESULTS: Glyceryl trinitrate decreased portal pressure from 14.0+/-1.1 to 11.8+/-1.4 mm Hg, splanchnic perfusion pressure from 102+/-10 to 74+/-5 mm Hg and portal sinusoidal flow from 2.11+/-0.38 to 1.70+/-0.35 ml/min/g liver (all p<0.05). Nitroprusside did not decrease portal pressure significantly but led to a reduction of the splanchnic perfusion pressure (104+/-9 to 66+/-7 mm Hg) and the portal sinusoidal flow (2.39+/-0.50 to 1.77+/-0.31 ml/min/g liver; all p<0.05). Portal sinusoidal resistance was not altered by either drug. CONCLUSIONS: Intraportal infusion of nitric oxide donors decreased arterial pressure more than portal pressure. Portal sinusoidal resistance remained unaffected, but the liver parenchyma became less perfused with high doses. The systemic effects of nitric oxide donating drugs prevailed.