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

BACKGROUND: Diuretic resistance and systemic hypotension are common in chronic heart failure (CHF), however, the two have not been associated. AIMS: Since blood pressure (BP) might be an important determinant of sodium excretion, we searched for an association between BP and diuretic dosage in severe CHF. METHODS: Our heart failure database was retrospectively reviewed for patients with severe left ventricular systolic dysfunction. The 54-patient cohort was divided on the basis of frusemide dosage (high-dose > or = 250 mg daily, n=26). RESULTS: Patients taking high-dose frusemide had higher serum creatinine, and lower systolic and diastolic BP. On logistic regression analysis, increased serum creatinine and reduced diastolic BP were independent predictors of the use of high-dose frusemide. Grouping these variables into tertiles, the odds ratio for the use of high-dose frusemide was 4.0 as diastolic BP decreased (p<0.01), and 6.8 as serum creatinine increased (p<0.001). CONCLUSIONS: We have found an association between hypotension and the use of high-dose frusemide in severe CHF, which is independent of renal function, and which may be an important physiologic mechanism of diuretic resistance in severe CHF.

Streptokinase morbidity--more common than previously recognised.

Streptokinase is the thrombolytic agent most commonly used for the treatment of acute myocardial infarction. We report eight patients who developed late uncommon adverse reactions to streptokinase probably due to immune complex disease. The clinical manifestations included vasculitic rashes, abnormal renal and liver function tests and a syndrome resembling adult respiratory distress syndrome. Major adverse events with streptokinase such as stroke, bleeding and other allergic reactions, have been previously documented but the morbidity related to delayed reactions has not been widely recognised. These reactions produced significant morbidity resulting in prolonged hospital stay and may need to be considered in the decision to use streptokinase.

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 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 baroreflex control of heart rate and myocardial contractility in conscious rabbits.

1. The effects of intravenous (i.v.) neuropeptide Y (NPY, 10 micrograms/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. 2. The relationship between increases and decreases in MAP and the subsequent changes in HP were represented by a sigmoid-shaped curve described by a logistic function. Following NPY administration there was a baroreflex-dependent increase in the maximum slope (sensitivity) at the midpoint of this MAP-HP curve from 7.0 +/- 0.5 to 10.6 +/- 1.3 ms/mmHg (P less than 0.05). NPY caused an upward shift in the whole curve which reflected the NPY-induced bradycardia and was independent of baroreflexes. 3. The relationship between increases in MAP and decreases in peak LV dP/dt was determined during fixed-rate atrial pacing to prevent the effects of the accompanying bradycardia. Increases in MAP and the corresponding reductions in peak LV dP/dt were represented by an exponential function. The slope of the curve, measured at its origin 5-15 min after NPY administration, was reduced from -0.9 +/- 0.2 to -0.4 +/- 0.1 units (P less than 0.05). 4. The effects of NPY are consistent with an action on efferent connections of the arterial baroreceptor reflex, mediated through a reduction in cardiac beta-adrenergic tone. They would also be explained through actions on the afferent or central neural connections of the baroreflex.

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

The direct and reflex-mediated components of the cardiovascular response to administration of neuro-peptide Y (NPY) in intact conscious rabbits were determined by studies with cardiac beta 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 micrograms/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 less than 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 less than 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 less than 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 beta-adrenergic tone and partly through a non-beta-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.

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. 2. Systolic blood pressure was underestimated by the TM-2420 by a mean of 10 mmHg (s.d. = 6, 95% confidence interval (CI) = -13 to -7) over the range of pressures measured by auscultation. It was underestimated by 23 mmHg (s.d. = 12, 95% CI = -28 to -18) compared with direct femoral artery measurements. 3. Diastolic pressure measurements were similar to those obtained by auscultation. When compared with direct femoral artery recordings, diastolic pressure was overestimated by about 5 mmHg (s.d. = 4, 95% CI = 3.4-6.6), which is consistent with indirect readings, taken with a 'standard' cuff (inflatable bladder 23 cm X 12 cm). 4. The TM-2420/2020 is thus suitable for ambulatory measurements of blood pressure when diastolic pressure is the criterion of interest.

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 micrograms/kg) were studied in the conscious rabbit. 2. NPY has a brief pressor effect associated with a bradycardia, an increase in left ventricular end diastolic pressure, and a prolonged fall in peak left ventricular dP/dt (LVdP/dt). 3. The haemodynamic changes increase substantially with increasing doses up to 10 micrograms/kg. Beyond 10 micrograms/kg there are only slight effects on heart rate or peak LV dP/dt.