Unmasking Individual and Institutional HIV Stigma in Hospitals: Perspectives of Dutch Healthcare Providers.

People with HIV continue to experience HIV stigma. Quantitative data on HIV stigma perpetrated by healthcare providers of hospitals providing HIV care in high-income countries are limited. The aim of this study is to investigate factors associated with HIV stigma in Dutch healthcare settings from the healthcare providers' perspective. We conducted a cross-sectional study using the questionnaire 'Measuring HIV Stigma and Discrimination Among Health Facility Staff - Monitoring Tool for Global Indicators' to assess HIV stigma among healthcare providers (n = 405) in two academic hospitals. Healthcare providers licensed to provide medical care were eligible for inclusion. The primary outcome was the self-reported prevalence of at least one manifestation of HIV stigma measured by six stigma indicators (four individual, two institutional). Secondary outcomes were the prevalence of HIV stigma per indicator, per occupation, per department, and factors associated with individual stigma indicators. HIV stigma was prevalent among 88.1% (95%CI 84.5% - 91.2%) of participants. Stigma was mostly driven by negative attitudes towards people with HIV and worry to acquire HIV. Multivariate analysis showed that several factors were associated with HIV stigma, including younger age, male sex, working at one of the surgical departments, and working as a nurse. Having received any training on HIV stigma and/or discrimination was associated with less HIV stigma among all indicators. In conclusion, HIV stigma is highly prevalent among Dutch healthcare providers. Targeted approaches, including training on HIV stigma and discrimination, are needed to reduce HIV stigma in healthcare and should, among others, focus on younger healthcare providers.

Captopril and angiotensin II receptor antagonist therapy in a pacing model of heart failure.

Twenty-four splenectomized dogs were subjected to rapid right ventricular pacing (RRVP) at 250 beats/min for five weeks. During the final three weeks, four groups six dogs were untreated or treated with captopril alone, with the angiotensin II type 1 (AT1) receptor antagonist L158,809 alone or with the two drugs combined by constant intravenous infusion. Hemodynamic studies were carried out during light anesthesia at baseline, and after two and five weeks of pacing. Total vascular capacitance and stressed blood volume were calculated from the mean circulatory filling pressure during transient circulatory arrest after acetylcholine administration at three different circulating volumes. Central blood volume and cardiac output were measured by thermodilution. Severe heart failure was present in the untreated group after five weeks of RRVP, characterized by low cardiac output and total vascular capacitance, high right atrial and pulmonary capillary wedge and mean circulatory filling pressure, plus increased stressed and central blood volumes. While L158,809 had not effect, captopril alone or combined with L158,809 ameliorated the reduction in total vascular capacitance, and reduced right atrial and mean circulatory pressure and stressed blood volumes. Combined therapy reduced pulmonary capillary wedge pressure. Thus, angiotensin-converting enzyme inhibition with captopril was effective in this model of chronic low output heart failure, whereas AT1 receptor antagonism was not.

CT-guided bone biopsy in a cancer center: experience with a new apple corer-shaped device.

In this article we report our experience with CT-guided bone biopsy (CTGBB) using a new nondisposable bone biopsy device with in a uniform protocol for all lesions and compare our results with data from bone biopsies obtained with other techniques. With this biopsy device, the specimen is collected in a 20 x 2 mm chamber of an apple corer-shaped needle. In 46 consecutive cancer patients that were candidates for bone biopsy, 50 CTGBB procedures were performed and analyzed. Lesions with cortical defects and/or surrounding soft tissue infiltration were excluded. There were no complications. Of 50 CTGBB procedures, 90% were diagnostic. Four of the five inconclusive biopsies were repeated: All were conclusive, one malignant. Of 19 with CT-indistinguishable lesions (detected on MRI or isotope studies), 35% were malignant. Thirty-eight percent of the lesions were not accompanied by pain. The procedure was less painful than injection of the local anesthetic prior to biopsy in 90% of the cases. With the new device, CTGBB procedures can be carried out safely. Biopsy with the described technique has a high diagnostic output, better results than those of biopsy with reported uniform techniques, and equal results to the best results of combined techniques. If a lesion is not distinguishable on CT and/or not accompanied by pain, malignancy is not ruled out. CTGBB in the described technique is less or equally time consuming, less painful, and cheaper than reported for other bone biopsy procedures.

ENT endoscopic surgical training simulator.

This paper describes work in progress on the design and development of a prototype simulator for minimally invasive otolaryngology surgical training. The anatomy of the paranasal sinuses is geometrically complex and dangerously close to the brain and orbits, making this procedure challenging to practice and difficult to learn. We discuss the potential role of computer simulation to enhance and accelerate acquisition of surgical skills. The design goals of the prototype include high-fidelity simulation of the endoscopic imagery and haptic cues of surgical palpation. The prototype enables endoscopic navigation and limited interactive tissue manipulation and dissection tasks on a virtual patient using realistic replicas of surgical tools. We present an overview of the system architecture with a discussion of the technological challenges, design issues and current status of the efforts.

Vascular capacitance and cardiac output in pacing-induced canine models of acute and chronic heart failure.

The relationship between stressed and total blood volume, total vascular capacitance, central blood volume, cardiac output (CO), and pulmonary capillary wedge pressure (Ppcw) was investigated in pacing-induced acute and chronic heart failure. Acute heart failure was induced in anesthetized splenectomized dogs by a volume load (20 mL/kg over 10 min) during rapid right ventricular pacing at 250 beats/min (RRVP) for 60 min. Chronic heart failure was induced by continuous RRVP for 2-6 weeks (average 24 +/- 2 days). Total vascular compliance and capacitance were calculated from the mean circulatory filling pressure (Pmcf) during transient circulatory arrest after acetylcholine at three different circulating volumes. Stressed blood volume was calculated as a product of compliance and Pmcf, with the total blood volume measured by a dye dilution. Central blood volume (CBV) and CO were measured by thermodilution. Central (heart and lung) vascular capacitance was estimated from the plot of Ppcw against CBV. Acute volume loading without RRVP increased capacitance and CO, whereas after volume loading with RRVP, capacitance and CO were unaltered from baseline. Chronic RRVP reduced capacitance and CO. All interventions, volume +/- RRVP or chronic RRVP, increased stressed and central blood volumes and Ppcw. Acute or chronic RRVP reduced central vascular capacitance. Cardiac output was increased when stressed and unstressed blood volumes increased proportionately as during volume loading alone. When CO was reduced and Ppcw increased, as during chronic RRVP or acute RRVP plus a volume load, stressed blood volume was increased and unstressed blood volume was decreased. Thus, interventions that reduced CO and increased Ppcw also increased stressed and reduced unstressed blood volume and total vascular capacitance.

Effect of perindopril in pacing-induced canine models of acute and chronic heart failure.

OBJECTIVE: To examine the effects of perindopril, a nonsulfhydryl-containing angiotensin-converting enzyme inhibitor, on total vascular capacitance and hemodynamics in acute and chronic dog models of heart failure. METHODS: Acute heart failure was induced in anesthetized, splenectomized dogs by a volume load (dextran 70, 20 mL/kg) during rapid right ventricular pacing (RRVP) at 250 beats/min. Pretreatment with perindopril (0.3 mg/kg daily for six days, n = 7) was compared with no treatment (n = 7). Total vascular capacitance and compliance were measured from plots of mean circulatory filling pressure during acetylcholine-induced circulatory arrests at different blood volumes. Chronic heart failure was induced by continuous RRVP in splenectomized dogs treated with perindopril (0.3 mg/kg daily, n = 8), which were compared with untreated dogs (n = 8). Hemodynamics and total vascular capacitance and compliance were measured at baseline and after 33 days of RRVP. RESULTS: Perindopril treatment did not significantly modify the increased pulmonary capillary wedge and mean circulatory filling pressures, reduced total vascular compliance or total vascular capacitance associated with the volume load and acute RRVP. During chronic RRVP, perindopril reduced weight gain and the development of ascites, reduced right atrial pressure (6.3 +/- 1.3 versus 10.3 +/- 1.2 mmHg), mean circulatory filling pressure (9.3 +/- 1.0 versus 14.7 +/- 1.2 mmHg), stressed blood volume (22 +/- 3 versus 33 +/- 4 mL/kg) and central blood volume (10 +/- 1 versus 14 +/- 1 mL/kg) while increasing cardiac output (122 +/- 9 versus 98 +/- 7 mL/kg). However, the reduction in total vascular capacitance was not attenuated and pulmonary capillary wedge pressure was not lowered significantly (18.5 +/- 1.5 versus 21.4 +/- 1.3 mmHg). CONCLUSION: Perindopril failed to modify hemodynamics in the pacing-induced canine model of acute heart failure but had beneficial effects in the model of chronic heart failure.

Acute effect of L-arginine on hemodynamics and vascular capacitance in the canine pacing model of heart failure.

The effect of L-arginine, 250 mg/kg over 10 min, on hemodynamics and venous function was studied in nine splenectomized dogs under light pentobarbital anesthesia before and after 17 +/- 1 days of rapid right ventricular pacing (RRVP) at 250 beats/min. Chronic RRVP induced mild congestive heart failure with increased mean circulatory filling (Pmcf), right atrial (Pra) and pulmonary capillary wedge pressures (Ppcw), and reduced cardiac output (CO). During the development of heart failure, total vascular compliance assessed from Pmcf-blood volume relationships during circulatory arrest was unchanged, but total vascular capacitance was markedly reduced, with an increase in stressed and reduction in unstressed blood volumes. At baseline but not after RRVP, L-arginine increased CO and reduced pulmonary vascular resistance. There were no significant changes in Pra, Ppcw, or total peripheral resistance. L-Arginine failed to alter total vascular compliance and capacitance or central blood volume in the baseline or failure state. These results do not support the hypothesis that increased Pmcf and reduced total vascular capacitance in the early stages of pacing-induced heart failure are caused by reduced substrate availability for or an endogenous competitive antagonist of NO synthase in venous endothelial cells.

Acute hemodynamic effects of drugs acting on the renin-angiotensin system in acute heart failure.

OBJECTIVE: To determine the role of the renin-angiotensin system in a model of acute heart failure. METHODS: Placebo or drugs (Ro 44-9375, a renin inhibitor; captopril, an angiotensin-converting enzyme [ACE] inhibitor; or DuP 532, an angiotensin II receptor [AT1] antagonist) were given to anesthetized splenectomized dogs (n = 12 for each group) for 50 mins after a volume load (dextran 70, 25 mL/kg over 10 mins) during rapid right ventricular pacing at 250 beats/min. Total vascular compliance and capacitance were determined from mean circulatory filling pressure-blood volume curves during transient circulatory arrests induced by acetylcholine. Cardiac index was measured by thermal dilution. RESULTS: Compared with the untreated group, all three drugs significantly reduced systemic pressure and total peripheral resistance while increasing arterial compliance. Captopril alone increased cardiac index (25 +/- 11 versus -23 +/- 13 mL/kg/min) and reduced pulmonary capillary wedge pressure (16.6 +/- 0.7 versus 21.9 +/- 1.0 mmHg). None of the drugs altered the mean circulatory filling pressure, total vascular compliance or capacitance, stressed or unstressed blood volumes, or central blood volume. CONCLUSION: The renin-angiotensin system is not strongly implicated in the hemodynamic manifestations of this model of acute heart failure. These drugs had effects on the arterial but not the venous side of the circulation. Captopril alone reduced pulmonary capillary wedge pressure, perhaps by nonangiotensin effects.

Effect of captopril treatment on total and central vascular capacitance in dogs with chronic heart failure.

Chronic rapid right ventricular pacing (RRVP) at 250 beats/min produces low cardiac output (CO) heart failure, marked reduction in total vascular capacitance, and a shift in volume centrally. The effect of converting enzyme inhibition with captopril on cardiac preload was investigated in this model of heart failure. Eight splenectomized dogs were treated with captopril (6.4 mg/kg daily) for 3 days before and 35 +/- 3 days (mean +/- SEM) after continuous RRVP was initiated and the outcome was compared with that of 5 untreated dogs subjected to RRVP for 32 +/- 3 days. Similar reductions in systemic arterial pressure (Psa) and CO and increases in right atrial pressure (Pra) and total peripheral resistance (TPR) were noted in both groups, however, pulmonary capillary wedge pressure (Ppcw) was higher in the untreated group (18.4 +/- 1.6 vs. 12.1 +/- 2.0 mm Hg). Total vascular compliance and capacitance was estimated from mean circulatory filling pressures (Pmcf) at different blood volumes (TBV) during transitory cardiac arrests with acetylcholine (ACh). Pmcf after chronic RRVP was higher in untreated animals (12.6 +/- 1.9 vs. 8.4 +/- 0.7 mm Hg) and compliance was lower (1.9 +/- 0.2 vs. 2.6 +/- 0.2 ml/mm Hg/kg). Total vascular capacitance at a Pmcf of 6 mm Hg was lower in untreated animals (50 +/- 6 vs. 68 +/- 3 ml/kg). Central vascular capacitance was also lower in untreated animals because Ppcw was higher and central blood volume (CBV) as a proportion of TBV was higher (21 +/- 3 vs. 15 +/- 2%). Four of 5 untreated and 1 of 8 treated dogs had severe ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril attenuates pacing-induced acute heart failure by increasing total vascular capacitance.

To study the effects of captopril pretreatment on vascular capacitance in acute heart failure, anesthetized splenectomized dogs were subjected to rapid right ventricular pacing (RRVP) at 250 beats/min for 60 min combined with an intravenous (i.v.) 20-ml/kg volume load of dextran 70 over 10 min. Captopril pretreatment [50 mg every 8 h for 3 days plus 0.5 mg/kg intravenously (i.v.) at induction of anesthesia] attenuated development of acute heart failure associated with RRVP, maintaining normal cardiac output (CO) and pulmonary capillary wedge pressures (PCWP). Total vascular capacitance after a volume load plus RRVP was higher in captopril-pretreated animals (129.8 +/- 3.2 vs. 100.4 +/- 4.8 ml/kg) owing to an increase in unstressed volume (118.6 +/- 3.1 vs. 88.4 +/- 5.6 ml/kg). Arterial capacity and pulmonary (central) vascular capacitance were also increased.

Acute effect of rapid ventricular pacing and volume loading on total vascular capacitance.

OBJECTIVE: Rapid right ventricular pacing (RRVP) at 250 beats/min plus a saline volume load produces acute heart failure manifested by a limited increase in cardiac output in response to the volume load and increased right atrial, pulmonary artery and capillary wedge pressures. The effects on vascular capacitance are unknown. DESIGN: Three groups of six anesthetized splenectomized dogs were subjected to RRVP alone at 250 beats/min for 40 mins volume loading alone with intravenous 0.9% sodium chloride 40 mL/kg over 10 mins or volume loading followed by RRVP for 15 mins. Vascular capacitance, unstressed volume and compliance were determined from pressure-volume curves using transient circulatory arrests induced by acetylcholine before and 40 mins after starting the interventions. RESULTS: Neither RRVP nor volume loading alone produced acute heart failure or altered total vascular compliance. Fifteen minutes of RRVP after the volume load induced heart failure, reduced compliance (3.4 +/- 0.5 to 2.5 +/- 0.3 mL/mmHg/kg, P < 0.05), increased central blood volume (7.7 +/- 0.7 to 10.6 +/- 0.5 mL/kg, P < 0.01) and reduced the unstressed vascular volume to 57 +/- 10 mL/kg, compared with 77 +/- 9 mL/kg (P < 0.01) after the volume load alone. Stressed blood volume was increased similarly with either volume loading alone (20.1 +/- 2.0 to 30.0 +/- 1.7 mL/kg, P < 0.01) or volume loading plus RRVP (23.5 +/- 3.8 to 30.2 +/- 4.9 mL/kg, P < 0.01). The reduction in unstressed volume rather than an increase in stressed volume was the major peripheral change associated with acute heart failure induced by volume loading plus RRVP. CONCLUSION: RRVP reduced vascular capacitance by a reduction in unstressed volume. Acute volume loading of this smaller vascular compartment resulted in redistribution centrally and acute heart failure.

Further evaluation of quantitative nuclear image features for classification of lung carcinomas.

The usefulness of quantitative nuclear image features (QNI) for the histological classification of lung carcinomas was investigated. As no clear distinction could be established between the distributions of these features for the nuclei of squamous cell, adenocarcinoma, and large cell carcinoma, the attention was restricted to the discrimination between small cell lung carcinoma (SCLC) and non-small cell carcinoma (NSCLC). This discrimination is the crucial one in discussions about the choice of treatment. The differences between SCLC and NSCLC are statistically highly significant for various QNI features. The use of more than one QNI feature hardly raised the discriminatory performance with respect to the distinction between SCLC and NSCLC. Inferences were made about the probability and confidence interval of SCLC for a given QNI feature. It is concluded that in cases of uncertainty or disagreement, nuclear characteristics are useful for the discrimination between SCLC and NSCLC.

The effects of cardiac transplantation and cyclosporine therapy on digoxin pharmacokinetics.

Most patients needing cardiac transplantation are treated with digoxin for heart failure. Because of its narrow therapeutic range, even recommended doses of digoxin may cause severe toxicity. Several drugs, including quinidine, amiodarone, verapamil, and propafenone can interact with digoxin, leading to toxic accumulation of the glycoside. The authors have recently reported two cases of severe digitalis toxicity after the initiation of cyclosporine treatment in patients awaiting cardiac transplantation. A preliminary study on two additional patients suggested that cyclosporine reduced the plasma clearance and volume of distribution of digoxin. To assess the mechanism of this interaction, the authors studied digoxin pharmacokinetics in patients awaiting cardiac transplantation and again after the surgery, during chronic cyclosporine therapy. To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were subsequently performed in dogs to allow controlled experimental conditions for evaluation of the digoxin-cyclosporine interaction.

Effect of chronic rapid ventricular pacing on total vascular capacitance.

BACKGROUND: Rapid right ventricular pacing (RRVP) at 250 bpm for 3-6 weeks produces chronic heart failure manifested by a reduction in cardiac output and increases in right atrial, pulmonary artery, and capillary wedge pressures. METHODS AND RESULTS: One week after splenectomy and pacemaker placement, vascular capacitance, unstressed volume, and compliance were determined in 19 anesthetized dogs from pressure-volume curves using transient circulatory arrests induced by acetylcholine. Nine dogs were restudied 31 +/- 1 days later without RRVP, and 10 dogs underwent RRVP at 250 bpm and were restudied at 23 +/- 8 and 38 +/- 8 days in cardiac failure and after 1 and 2 weeks of postpacing recovery. Control animals had no changes in vascular capacitance or compliance. Dogs undergoing RRVP exhibited a marked increase in mean circulatory filling pressure (5.4 +/- 0.4 to 10.5 +/- 1.5 mm Hg) during the development of cardiac failure with a reduction in unstressed volume (81.9 +/- 5.7 to 43.9 +/- 8.1 ml.kg-1) without changing total vascular compliance. Total blood volume decreased (95.4 +/- 6.2 to 66.7 +/- 6.5 ml.kg-1) primarily due to a reduction in packed cell volume. The pressure gradient for venous return and overall venous resistance was unaltered. Central blood volume as a proportion of total blood volume increased (9.3 +/- 1.7% to 16.0 +/- 2.7%). Arterial compliance and capacity and pulmonary vascular compliance were reduced. In the 2-week postpacing period, except for a reduced cardiac response to a volume load, all of these parameters returned to baseline values. CONCLUSIONS: Chronic RRVP induced cardiac failure with a marked reduction in total vascular capacitance due to a reduction in unstressed volume without altering compliance. The rise in mean circulatory filling pressure was limited by a reduction in total blood volume.

Effects of nitroglycerin and nitroprusside on vascular capacitance of anesthetized ganglion-blocked dogs.

To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after increases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 +/- 1.4 ml/kg after NTG and 3.0 +/- 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

Measurement of mean circulatory filling pressure and vascular compliance in domestic pigs.

To measure mean circulatory filling pressure (Pmcf), a balloon was placed in the right atrium of seven pentobarbital sodium-anesthetized open-chest pigs for transient occlusion of flow combined with mechanical transfer of blood from the arterial to the venous circulation. Equilibration occurred within 6-8 s at a pressure at 12.3 +/- 0.3 (SE) mmHg after a 2.9 +/- 0.2 ml/kg transfer of blood. In another group of pentobarbital sodium-anesthetized closed-chest pigs, acetylcholine (ACh) was used to induce cardiac arrest. The Pmcf was 11.6 +/- 1.0 mmHg in the 7:17 pigs that arrested for 6-8 s. In four isoflurane-anesthetized closed-chest pigs, the Pmcf was 12.0 +/- 1.0 mmHg after terminal cardiac arrest induced by KCl. The pressure gradient for venous return [Pmcf--right atrial pressure (Pra)] averaged 5.9 +/- 0.2 mmHg. Total vascular compliance estimated from plots of Pmcf at base line, 5, and 10 ml/kg increases in circulating volume was 2.1 +/- 0.3 and 3.5 +/- 0.9 ml.kg-1.mmHg-1 in the balloon and ACh groups, respectively compared with 2.8 +/- 0.4 ml.kg-1.mmHg-1 using a volume infusion-withdrawal method without circulatory arrest. The use of ACh for the estimate of Pmcf in the pig is not recommended because of failure to consistently induce circulatory arrest and probable failure to achieve sufficient equilibrium of vascular pressures 6-8 s postarrest when it occurs.

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.

Analysis of venous flow transients for estimation of vascular resistance, compliance, and blood flow distribution.

We analysed venous flow transients using a long venous circuit and right heart bypass in 17 dogs after a rapid decrease in atrial pressure. A biphase curve was obtained which we decomposed into a two-compartment model, one with a fast time constant for venous return (0.069 min) and 52% of total circulating flow (Q), and one with a slower time constant (0.456 min) and 48% of Q. Subsequently, separate drainage from splanchnic and peripheral beds (with the renal venous return in the peripheral bed drainage) allowed comparison of time constants and venous outflow in these beds. The sum of the venous outflow volumes over time during separate drainage was indistinguishable from the single biphasic venous outflow volume curve over time observed with a long circuit and single reservoir. The fast time constant of the biphasic curve was not different from that determined by separate drainage from the peripheral circulation. The slow time constant of the single biphasic curve of 0.456 min was hybrid of two time constants, 0.216 min in the splanchnic bed and 0.862 min in the peripheral bed. Separate drainage from peripheral and splanchnic vascular beds demonstrated that the peripheral bed constituted 70% of venous outflow in the fast time constant compartment using Caldini's technique, whereas the splanchnic bed constituted 63% of venous outflow in the slow time constant compartment. It is concluded that, although Caldini's technique demonstrates biphasic venous flow transients, neither the fast nor the slow time constant compartments resolved from this analysis represent a particular anatomical region or vascular bed.

Compartmental vascular changes in dogs after nephrectomy, DOCA, and saline: effect of nifedipine.

Hypertension (mean arterial pressure, (MAP) 131 +/- 3 mmHg) developed in 18 dogs 4 weeks after left nephrectomy, deoxycorticosterone acetate (DOCA), 5 mg/kg sc twice weekly), and 0.5% NaCl drinking solution. This can be compared with MAP (95 +/- 7 mmHg) of 13 dogs with nephrectomy alone and MAP (86 +/- 4 mmHg) of dogs without nephrectomy. The two-compartment model of the circulation revealed no differences in systemic vascular compliance, compartmental compliance, or flow distribution to the compartments. However, the time constant for venous return for the compartment with the rapid time constant was increased from 0.05 +/- 0.004 min in control animals to 0.07 +/- 0.006 min in the nephrectomy alone group and 0.09 +/- 0.008 min in the hypertensive group (p less than 0.001), as a result of an increase in venous resistance. Arteriolar resistance in this compartment was also increased in the hypertensive animals, as was the mean circulatory filling pressure and overall resistance to venous return. Nifedipine (0.025-0.05 mg/kg) reduced MAP by 15% in the nephrectomy alone group and by 22% in the hypertensive group, with reduction in arteriolar resistance only in the fast time constant compartment. In the slow time constant compartment, arteriolar resistance was increased by more than 100% and flow decreased by more than 50% after nifedipine. Unilateral nephrectomy, DOCA, plus NaCl resulted in hypertension by increasing arteriolar resistance in a vascular compartment with a fast time constant for venous return. Nifedipine countered this effect by inducing arteriolar vasodilation in this compartment. In addition, nifedipine reduced the mean circulatory filling pressure and overall resistance to venous return.

Effects of oral perhexiline on canine myocardial flow distribution.

Perhexiline maleate at a dose of 400 mg three times daily for 2 days administered to normal dogs altered the relative regional transmural resistance so that during reduced coronary flow the endocardium:epicardium (endo:epi) ratio is increased. In the presence of acute myocardial infarction heart rate was significantly lower and the endo:epi ratio of perfused areas was increased when coronary flow was normal. A linear relationship was observed between the endo:epi ratio and the concentration of perhexiline in plasma, and its monohydroxyl metabolite in plasma. The results suggest that the mechanism of action of the drug is due to redistribution of a limited coronary flow.