Retrograde infusion of blood into a pulmonary vein promotes natriuresis in anaesthetized dogs.

Retrograde infusion of blood into a pulmonary vein raised the pressure by 0.5-1 kPa in the cannulated vein. There were no changes in heart rate, arterial blood pressure, left atrial pressure, right atrial pressure or the pressure in the other pulmonary veins. The rise in pulmonary venous pressure was associated with an increase in urinary sodium concentration and excretion. However, there was no change in urine volume. The natriuresis was abolished by cooling the vagi to 9 degrees C. It is argued that receptors up-stream in the pulmonary veins themselves may be involved in the increase in sodium excretion that follows a rise in left atrial pressure.

Class III action of beta-blocking agents.

We have studied the effect of the intravenous administration of the following drugs on ventricular refractoriness in 35 experiments in open chested beagle dogs: atenolol 0.2 mg X kg-1; nadolol 0.05 mg X kg-1; oxprenolol 0.2 mg X kg-1; pindolol 0.04 mg X kg-1; propranolol 0.2 mg X kg-1; sotalol 0.6 mg X kg-1 and timolol 0.1 mg X kg-1. The animals were anaesthetised with chloralose and urethane. Measurements were made of left ventricular epicardial monophasic action potentials (MAP) (n = 35) and the left ventricular paced evoked response (PER) (n = 25) at a fixed paced cycle length of between 220 and 310 ms. The animals were initially beta-blocked with iv pindolol or propranolol and the drug under study then administered iv 10 min later. The results were as follows: (control and post drug administration) MAP: nadolol 151 +/- 12 SD to 172 +/- 13 SD (p less than 0.001); oxprenolol 153 +/- 21 to 178 +/- 20 (p less than 0.001); sotalol 153 +/- 19 to 176 +/- 20 (p less than 0.001); atenolol 152 +/- 25 to 153 +/- 23 (NS); pindolol 149 +/- 11 to 152 +/- 10 (NS); propranolol 152 +/- 26 to 155 +/- 26 (NS); timolol 144 +/- 23 to 144 +/- 21 (NS). PER: nadolol 172 +/- 14 to 190 +/- 20 (p less than 0.001); oxprenolol 164 +/- 16 to 188 +/- 15 (p less than 0.001); propranolol 166 +/- 22 to 173 +/- 18 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of ischaemia and hyperkalaemia on myocardial repolarization and conduction times in the dog.

The role of increased extracellular K+ concentration ([K+]o) in the production of the early electrophysiological changes induced by myocardial ischaemia, was evaluated by recordings of monophasic action potentials and the paced endocardial evoked response. Changes in the duration of local repolarization and conduction time were evaluated during ischaemia, K+ infusion and hypoxia. Raising [K+]o levels in systemic arterial blood from 3.4 +/- 0.5 mmol l-1 to 5.9 +/- 1.5 mmol l-1 produced a similar shortening of repolarization as was seen during ischaemia. Prolongation of conduction time occurred only when the [K+]o levels rose to 8.8 +/- 1.3 mmol l-1. The conduction time slowing during acute ischaemia was always greater and occurred at lower [K+]o levels than that produced by K+ infusion at rates equivalent to the post-ischaemic myocardial venous effluent. Monophasic action potential amplitude and upstroke velocity were reduced in ischaemia but not markedly affected by the increase in [K+]o. Absolute reduction in repolarization time during K+ infusion was more marked at the apex than at the base in the epicardial recordings. The superimposition of hypoxia on hyperkalaemia resulted in marked slowing of repolarization and conduction time. Many but not all of the early electrophysiological abnormalities of acute ischaemia in the intact heart can be related to raised [K+]o.

Recordings of the local pacing-induced myocardial activation and repolarization.

We have studied the endocardial ventricular evoked response which follows delivery of a unipolar stimulus down the sensing electrode. The system uses the same lead for both pacing and sensing and permits recordings of the evoked T wave representing a dominantly local repolarization which follows a pacing-induced depolarization at the same site. In 12 animal experiments and in the course of electrophysiological investigations in 19 patients, we evaluated changes in the morphology and duration of the paced evoked response following drug interventions which alter myocardial refractoriness and repolarization time. These changes paralleled results obtained by simultaneous, paced monophasic action potential recordings, and suggest that myocardial repolarization can be accurately assessed by this new technique, which could overcome some of the difficulties in comparing 'in vivo' experiments with the clinical effects of drugs in man.

Study of the electrophysiological effects of early or subendocardial ischaemia with intracavitary electrodes in the dog.

The early electrophysiological patterns of regional subendocardial ischaemia were studied by using the paced endocardial evoked response and simultaneous endocardial monophasic action potential recordings in 16 experiments in open chested dogs. Ischaemia was produced by transient (1-3 min) coronary artery occlusion. Regional subendocardial isochaemia caused asynchronous activation due to differential conduction delay and shortened repolarization as evaluated by the duration of the paced evoked response from 175 +/- (SD) 18.7 ms to 167 +/- 16 ms (P less than 0.001). These changes occurred within 60 s of occlusion and reversed rapidly after release of the occlusion. In simultaneous endocardial monophasic action potentials there was a decrease in plateau amplitude and the duration of repolarization shortened from 180 +/- (SD) 21.2 ms to 167 +/- 20.4 ms (P less than 0.001). The delay in endocardial activation after 2 min ischaemia was 5.5 ms, which is considerably shorter than the conduction delay previously reported in the subepicardial layers. The calcium-channel blocking drug verapamil (infused at 0.4 mg/kg) altered the rate at which shortening of repolarization and asynchronous activation occurred during ischaemia in six experiments. These experiments suggest that intracavitary electrodes could provide earlier and more sensitive detection of regional subendocardial ischaemia and may permit the assessment of therapy on the early electrical changes in the intact heart.

An analysis of the regulation of sodium excretion during induced changes in plasma sodium concentration in anaesthetized dogs.

1. Renal sodium excretion (UNaV) was studied during acute changes in plasma sodium concentration (PNa) induced by altering the concentration of a sodium chloride infusion in anaesthetized dogs. 2. The change in PNa induced other changes, notably in blood pH, the degree of blood dilution, and in glomerular filtration rate and renal plasma flow. No attempt was made to restrain these changes and their effects on UNaV were assessed using factor analysis. This defined new variables ('factors') that are linear functions of the primary variables. Four factors were defined, two of which were related to UNaV. 3. Factor 1 was strongly correlated with UNaV and PNa: its other correlations described the acidosis and plasma dilution of hypernatraemia. Further examination of these inter-relationships by regression analysis and data selection showed that the increase in UNaV with rising PNa depended upon a fall in both the blood pH and PCO2. 4. Factor 2 was negatively correlated with UNaV: its correlations with plasma protein concentration, haematocrit, blood pressure, glomerular filtration rate and renal plasma flow implied that it represented post-glomerular plasma protein concentration and its influence on sodium reabsorption. 5. Thus, two independent processes may regulate UNaV during acute salt loading: one is initiated by changes in PNa and plasma dilution but requires a concomitant acidosis and ventilatory adjustment for its full expression; the second relates UNaV to several variables whose influences could be understood by changes they produce in the peritubular capillary plasma protein concentration.

An examination of the xenon clearance method.

A definition of cortical and juxta-medullary regions is suggested based on a grouping of nephrons of common flow characteristics. A possible error is suggested in the xenon clearance method of measuring the regional flows. Experiments to test the source of error and its magnitude are described. It is concluded that while the error is present its effect on conventional component analysis is small.

The renal blood flow and the glomerular filtration rate of anaesthetized dogs during acute changes in plasma sodium concentration.

1. The effects of acute changes in plasma Na concentration (P(Na)) on renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in anaesthetized greyhounds. Saline was infused at a constant rate (0.1 ml. kg(-1) min(-1)) either into a renal artery or into a systemic vein. Plasma Na concentration was altered by varying the Na concentration of the infused saline from 0.154 to 0.077, 0.616 or 1.232 M.2. Blood pressure (B.P.), packed cell volume (PCV), concentration of plasma solids (PS) and the plasma concentration of H(+) and K (P(K)) ions were measured but no attempt was made to contain their fluctuation.3. An infusion of hypertonic saline into a renal artery usually led to an ipsilateral increase in RBF for 5-15 min, followed by a progressive fall. Over-all, mean values of RBF fell with P(Na) throughout the range studied (120-190 m-mole l.(-1)). Glomerular filtration rate rose with P(Na) to reach maximal values at P(Na) levels of 140-160 m-mole l.(-1), but fell thereafter. The combined fall in RBF and GFR, without change in filtration fraction, at P(Na) values above 160 m-mole l.(-1) is consistent with an alteration in afferent arteriolar resistance. The fall in GFR despite a rise in RBF noted when P(Na) was reduced below 140 m-mole l.(-1) requires an additional explanation.4. Renal blood flow was independent of P(K); it was inversely related to [H(+)] and directly related to PS. Glomerular filtration rate was independent of PCV and P(K). It was also inversely related to [H(+)] and directly related to PS up to a value of 6 g 100 g(-1) plasma, after which the relationship was reversed. These results suggest that the renal vascular responses to acute changes in P(Na) may be mediated in part, at least, by concurrent change in PS and [H(+)].

Plasma sodium concentration and sodium excretion in the anaesthetized dog.

1. The effect of acute alterations of plasma sodium concentration (PNa) on renal sodium excretion (UNaV) was investigated by three types of experiments on anaesthetized dogs: (a) A local increase in PNa at one kidney was produced by infusion of hypertonic saline directly into its artery while systemic levels of PNa were stabilized by haemodialysis. (b) Systemic levels of PNa were lowered by exchange transfusion of blood for an equal volume of salt-free dextran-in-dextrose solution. The results were contrasted with those observed after similar exchanges, but using dextran-in-saline solution. (c) The level of PNa was altered by varying the sodium concentration of a saline solution infused at a fixed rate either intravenously or into one renal artery. 2. All three types of experiment suggest a dependence of UNaV on PNa Analysis demonstrated that this relationship was not due to contemporary changes in: packed cell volume; plasma solids concentration; plasma potassium concentration; blood pressure or plasma hydrogen ion concentration. The distribution of these variables did not change with PNa except for plasma hydrogen ion concentration. Moreover, the relationship persisted when data were selected to exclude clearance periods in which the value for any variable had shifted past the group mean obtained before PNa was altered. 3. The fall in UNaV at low levels of PNa could be attributed to a fall in glomerular filtration rate (GFR), but the progressive rise in UNaV seen as PNa exceeded 150 m-mole 1(-1) occurred despite a fall in GFR and no apparent change in the mean filtered load of sodium. These results suggest that the increased sodium excretion accompanying raised levels of PNa is due to reduced tubular re-absorption of sodium.