R. B. Minson

Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

IntroductionPulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.MethodsPatients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.ResultsAmong 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.ConclusionsIn this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.

Automated non-invasive measurement of cardiac output by the carbon dioxide rebreathing method: comparisons with dye dilution and thermodilution.

The accuracy and reproducibility of indirect measurement of cardiac output at rest by the carbon dioxide rebreathing (indirect Fick) method with an automated respiratory analysis system (Gould 9000IV) were compared with simultaneous measurements made in duplicate by dye dilution and thermodilution in 25 patients having cardiac catheterisation studies. Measurements of cardiac output by the carbon dioxide rebreathing method were not significantly different from those obtained with dye dilution (mean difference -0.3 l/min, SD 0.76, 95% confidence interval -0.7 to 0.1). Thermodilution significantly over-estimated cardiac output by a mean of 2.2 l/min or 39% (SD 1.5, 95% confidence interval 1.6 to 2.8) compared with the carbon dioxide rebreathing method and significantly overestimated cardiac output by 1.9 l/min or 31% (SD 1.2, 95% confidence interval 1.2 to 2.5) compared with dye dilution. The reproducibility of measurements of cardiac output in individual patients was satisfactory with the dye dilution method but was poor with carbon dioxide rebreathing and thermodilution. Indirect measurement of resting cardiac output by the Gould 9000IV automated carbon dioxide rebreathing method is more accurate but the variability inherent with this method requires that multiple measurements be taken for each determination. Measurement of cardiac output by the thermodilution method by a commercially available cardiac output computer was not satisfactory because not only was there considerable variability between repeat measurements but the method also consistently overestimated cardiac output compared with the dye dilution method.

Effects of neuropeptide Y on the renal mesenteric and hindlimb vascular beds of the conscious rabbit

The effects of neuropeptide Y (NPY, 10 micrograms/kg bolus i.v.) on renal, mesenteric and hindlimb blood flow were determined in intact conscious rabbits with chronically implanted Doppler ultrasonic flow transducers. The role of sympathetic neuro-effectors was assessed using inhibition of peripheral alpha-adrenoceptors with phentolamine in each group, and in the renal flow group following chemical sympathectomy with 6-hydroxydopamine. In controls, NPY caused markedly non-uniform peak responses. Renal blood flow fell from 2.16 +/- 0.12 kHz to a minimum of 0.26 +/- 0.07 kHz following NPY administration (P less than 0.05). Mesenteric blood flow was reduced from 2.04 +/- 1.17 to 1.54 +/- 0.11 kHz (P less than 0.05). blood flow increased transiently from 2.33 +/- 0.15 to a peak of 3.33 +/- 0.19 kHz (P less than 0.05). Renal vascular resistance rose by 1189 +/- 309% and mesenteric resistance by 54 +/- 9% (P less than 0.05), while hindlimb resistance fell by 24 +/- 3% (P less than 0.05). Pretreatment with phentolamine accentuated the peak pressor response and the reduction in heart rate induced by NPY administration but had little effect on the local haemodynamic changes in each vascular bed. There was no change in the renal vascular response to NPY following sympathectomy. Indeed, the peak NPY-induced reduction in renal blood flow seen in control animals (87 +/- 4%) was unaffected by either alpha-adrenoceptor inhibition (90 +/- 5%) or by sympathectomy (86 +/- 5%). In conscious rabbits with intact cardiovascular reflexes, pharmacological doses of NPY cause profound renal vasoconstriction with smaller changes in mesenteric and hindlimb flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypotension is associated with diuretic resistance in severe chronic heart failure, independent of renal function

Diuretic resistance and systemic hypotension are common in chronic heart failure (CHF), however, the two have not been associated.

Effects of neuropeptide Y on cardiac performance and renal blood flow in conscious normotensive and renal hypertensive rabbits

The effects of neuropeptide Y (NPY, 10 micrograms/kg bolus iv) on cardiac output, renal blood flow and myocardial contractility were determined in intact renal hypertensive and normotensive rabbits instrumented with ultrasonic flow transducers or left ventricular catheters. The basal plasma concentration of NPY-like immunoreactivity in arterial blood was greater in the hypertensive rabbits (4.2 +/- 0.7 micrograms/l) than in normotensive animals (2.2 +/- 0.4 micrograms/l, p less than 0.05). There were similar moderate increases in arterial blood pressure and total peripheral resistance following NPY, but a small NPY-induced reduction in cardiac output in normotensive rabbits was not seen in hypertensive animals. Resting peak left ventricular dP/dt (an index of myocardial contractility) was higher in hypertensive rabbits (7397 +/- 619 vs 5551 +/- 342 mmHg/sec, p less than 0.05), but there was no significant difference between the maximum NPY-induced falls in peak dP/dt. NPY produced significant peak reductions in renal blood flow in both hypertensive (from 2.5 +/- 0.2 to 1.2 +/- 0.2 kHz, p less than 0.05) and in normotensive rabbit groups (from 2.2 +/- 0.1 to 0.3 +/- 0.1 kHz, p less than 0.05), but the fall in renal blood flow and the corresponding rise in renovascular resistance were smaller in the hypertensive animals (p less than 0.05). The cause of this apparent decrease in renovascular reactivity in the renal hypertensive model was not determined.

Effects of neuropeptide Y on the heart and circulation of the conscious rabbit.

Summary: The direct and reflex-mediated components of the cardiovascular response to administration of neuropeptide Y (NPY) in intact conscious rabbits were determined by studies with cardiac β adrenoceptor and vagal blockade, and during total autonomic blockade. Cardiac pacing was used to prevent bradycardia, and sinoaortic denervation (SAD) was used to remove afferent baroreflex input. In control animals, NPY (10 μg/kg bolus i.v.) caused arterial pressure to increase from 77.4 ± 1.5 mm Hg (mean ± SEM) to a maximum of 91.4 ± 1.6 mm Hg (p < 0.05). This pressor response was independent of autonomic effectors but was buffered by arterial baroreflexes. The fall in heart rate (HR) from 281 ± 14 to 252 ± 18 beats/min (p < 0.05) was mediated in part through baroreceptor-dependent changes in cardiac autonomic efferent activity, but was in part independent of autonomic neural mechanisms. Peak left ventricular (LV)dP/dt fell from 5,551 ± 342 to 4,182 ± 394 mm Hg/s (p < 0.05) following NPY in control rabbits. This reduction was maintained during pacing and following SAD, and was caused partly by a withdrawal of cardiac β-adrenergic tone and partly through a non-β-mediated myocardial depression. Small changes in cardiac output (CO) and in LV end-diastolic pressure (LVEDP) after NPY were secondary to bradycardia. Total autonomic blockade did not impair the NPY-induced rise in total peripheral resistance (TPR), suggesting a direct vasoconstrictor action that was independent of neural mechanisms.

Effects of neuropeptide Y on baroreflex control of heart rate and myocardial contractility in conscious rabbits

1. The effects of intravenous (i.v.) neuropeptide Y (NPY, 10 μg/kg bolus) on the stimulus‐response curves relating changes in heart period (HP) and in peak left ventricular (LV) dP/dt to acute changes in mean arterial pressure (MAP) were determined in conscious, normotensive rabbits.

Effects of neuropeptide Y on left ventricular function in the conscious rabbit

1. Changes in arterial pressure, heart rate and left ventricular contractility induced by intravenous injections of neuropeptide Y (NPY; 1–30 μg/kg) were studied in the conscious rabbit.

Accuracy of the takeda TM-2420 ambulatory blood pressure monitor

1. The accuracy of blood pressure measurement with the Takeda TM‐2420 ambulatory blood pressure monitor and the TM‐2020 data recorder have been assessed by comparison with simultaneous measurements taken using auscultation and direct femoral artery measurements.