Effects of acute changes in load and inotropic state on the exponential rate of fiber shortening and other indices of myocardial contractility in the anesthetized intact dog

The effects of an acute increase in preload, afterload, and inotropic state on several indices of left ventricular contractility were studied in 20 anesthetized intact dogs. The behaviour of the exponential rate of fiber shortening (ERFS), a newly described index, which is based on the instantaneous fiber length--time relationship through ejection, was compared with other classical ejection and isovolumic indices of left ventricular contractility. Acute volume overload by dextran 40 infusion produced a significant increase in preload as reflected by a 103% (p less than 0.01) increase in left ventricular end-diastolic pressure and a 121% (p less than 0.001) increase in end-diastolic circumferential wall stress. There was also a smaller but significant increase (p less than 0.05) of heart rate (30%) and of peak systolic circumferential wall stress (24%). None of the left ventricular contractility indices showed any significant change. Acute pressure overload, produced mechanically by an aortic balloon, increased the afterload significantly as reflected by a 33% (p less than 0.05) rise of end-systolic circumferential wall stress and a 43% (p less than 0.001) increase in systemic resistance. Stroke volume decreased significantly by 23% (p less than 0.05). All ejection indices, including ERFS, were significantly diminished by 30-37%; all isovolumic indices showed no significant changes. Positive inotropic intervention was induced by dopamine infusion, which caused a significant 28% (p less than 0.05) increase in cardiac output. End-diastolic and end-systolic circumferential wall stress were significantly diminished. All indices of left ventricular contractility increased significantly and ERFS showed the quantitatively greatest change.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of prolonged infusion and withdrawal of angiotensin II in the spontaneously hypertensive rat

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 microgram X kg-1 X min-1 for 3h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 +/- 3.3 to 146 +/- 3.9 mmHg (p less than 0.01), whereas pressure in WKY had fallen from 116 +/- 3.0 to 107 +/- 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p less than 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.     

Exercise stroke volume relative to plasma-volume expansion

The effects of plasma-volume (PV) expansion on stroke volume (SV) (CO2 rebreathing) during submaximal exercise were determined. Intravenous infusion of 403 +/- 21 ml of a 6% dextran solution before exercise in the upright position increased SV 11% (i.e., 130 +/- 6 to 144 +/- 5 ml; P less than 0.05) in untrained males (n = 7). Further PV expansion (i.e., 706 +/- 43 ml) did not result in a further increase in SV (i.e., 145 +/- 4 ml). SV was somewhat higher during supine compared with upright exercise when blood volume (BV) was normal (i.e., 138 +/- 8 vs. 130 +/- 6 ml; P = 0.08). PV expansion also increased SV during exercise in the supine position (i.e., 138 +/- 8 to 150 +/- 8 ml; P less than 0.05). In contrast to these observations in untrained men, PV expansion of endurance-trained men (n = 10), who were naturally PV expanded, did not increase SV during exercise in the upright or supine positions. When BV in the untrained men was increased to match that of the endurance-trained subjects, SV was observed to be 15% higher (165 +/- 7 vs. 144 +/- 5 ml; P less than 0.05), whereas mean blood pressure and total peripheral resistance were significantly lower (P less than 0.05) in the trained compared with untrained subjects during upright exercise at a similar heart rate. The present findings indicate that exercise SV in untrained men is preload dependent and that increases in exercise SV occur in response to the first 400 ml of PV expansion. It appears that approximately one-half of the difference in SV normally observed between untrained and highly endurance-trained men during upright exercise is due to a suboptimal BV in the untrained men.     

Respiratory depression produced by centrally administered taurine in the cat

The effects of taurine (0.8-64.8 mumol) were studied on respiratory activity following intracisternal (cisterna magna) and intracerebroventricular (lateral ventricle) injections in cats anesthetized with alpha-chloralose. Respiratory activity was measured by using a Fleisch pneumotachograph and monitoring tracheal airflow. The flow signal was integrated to obtain tidal volume (VT) and respiratory rate (f) was obtained by counting the number of VT excursions over one minute. Inspiratory (TI), expiratory (TE) and total (TTOT) cycle durations were also determined during this time period. In addition, end-tidal CO2 was continuously monitored. Associated changes in arterial pressure (femoral artery cannula) and heart rate were also determined. After injections into the cisterna magna, taurine caused dose-related decreases in minute ventilation (VE). The maximal decrease in VE was from 495 +/- 59 to 64 +/- 14 ml/min (p less than 0.05), and was due to both decreases in VT (from 27 +/- 3 to 5 +/- 1 ml; p less than 0.05) and f (from 18 +/- 1 to 12 +/- 2 breaths/min; p less than 0.05). TE and TTOT were increased from 2.4 +/- 0.4 to 4.5 +/- 0.6 sec (p less than 0.05) and from 3.7 +/- 0.4 to 6.4 +/- 0.8 sec (p less than 0.05), respectively. Mean inspiratory flow (VT/TI), a measure of inspiratory drive, was decreased from 21 +/- 4 to 4 +/- 2 ml/sec (p less than 0.05). Apnea occurred in 5 of 6 animals after the 64.8 mumol dose. This respiratory depression occurred without any significant change in arterial pressure. After lateral ventricle injections, taurine also caused dose-related, but not as pronounced, decreases in respiratory activity. In addition, taurine caused significant decreases (p less than 0.05) in arterial pressure in doses that decreased VE. Taurine administered intravenously had no significant cardiorespiratory depressant effects. These data indicate that centrally administered taurine produces respiratory depression and, depending on the route of CNS administration, also produces hypotension.     

Role of the pituitary in the effects of tonin on adrenal secretion of the rat

Chronically catheterized conscious rats were infused intravenously with tonin at 2.4 and 12 micrograms x kg-1 x min-1 for 2 h. Plasma aldosterone concentration (PAC) at the end of the experiment was 11.2 +/- 2.4 ng% in controls, 8.5 +/- 2.8 ng% in rats infused with tonin at the lower rate, and 26.2 +/- 3.6 ng% (p less than 0.01 vs. controls) in rats infused at the higher rate. Plasma corticosterone (PC) was significantly higher (p less than 0.05) in the group infused at the high rate while plasma renin activity (PRA) was significantly reduced in this group of rats. Plasma angiotensin II (AII) concentration was similar in all three groups. PAC was elevated after tonin infusion in the presence of AII blockade. PAC in conscious sodium-depleted rats infused with tonin was not significantly changed, but PRA was significantly reduced (p less than 0.01). In chronically hypophysectomized rats, PAC remained unchanged by tonin infusion. The failure of tonin to stimulate aldosterone in hypophysectomized animals indicates a role of a pituitary hormone (probably ACTH) in the effect of tonin on adrenal secretion.     

Effects of atrial natriuretic factor on maternal ovine vascular resistance

Atrial natriuretic factor (ANF) is a potent endogenous vaso-dilator and diuretic peptide of uncertain physiologic relevance. In this study, the effects of ANF on normal and angiotensin II constricted placental, uterine and renal vessels were examined in pregnant sheep. Ewes were equipped with catheters to monitor vascular pressures, infuse drugs and measure blood flow by the microsphere technique. An electromagnetic flow sensor was placed around the middle uterine artery and electromyogram electrodes were attached to the uterus. ANF was administered into a branch of the uterine artery to minimize its systemic effects. The experiment included two protocols. First, blood flows and pressures were measured after a 5-min period of saline infusion into the uterine artery. These measurements were repeated at the end of a 5-min infusion of ANF (6.25 micrograms.min-1) into the uterine artery. During the second protocol, angiotensin II (AII) was infused via the jugular vein at 5 micrograms.min-1 for 10 min and ANF (6.25 micrograms.min-1) was infused through the uterine artery during the second half of the AII infusion. In the absence of AII, ANF lowered blood pressure from 97 +/- 6 to 90 +/- 6 mmHg (P less than 0.05); and placental resistance from 67.8 +/- 11.3 to 57.3 +/- 10.4 mmHg.min.ml-1 per g (P less than 0.01). Uterine resistance did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility.

Positive pleural pressure (Ppl) decreases left ventricular afterload and preload. The resulting change in cardiac output (CO) in response to these altered loading conditions varies with the baseline level of cardiac contractility. In an isolated canine heart-lung preparation, we studied the effects of positive Ppl applied phasically during systole or diastole on CO and on the cardiac function curve (the relationship between CO and left atrial transmural pressure). When baseline cardiac contractility was enhanced by epinephrine infusion, systolic and diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and 1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the pressure gradient driving venous return. However, neither shifted the position of the cardiac function curve, suggesting that the predominant effect of positive Ppl was decreased preload. When baseline cardiac contractility was depressed by severe respiratory acidosis, diastolic positive Ppl pulses caused no significant change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or the pressure gradient for venous return. However, systolic positive Ppl pulses increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and significantly shifted the cardiac function curve to the left. Thus the effect of Ppl pulsations on CO works through different mechanisms, depending on the state of cardiac contractility.     

Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat

Prostaglandin E2, when infused into the renal artery of the dog, is a vasodilator and increases both renal interstitial hydrostatic pressure and sodium excretion. Similar studies in the rat, however, have been inconclusive. The present study examined the effect of prostaglandin E2 infusion into the renal interstitium, by means of a chronically implanted matrix, on renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. Prostaglandin E2 was continuously infused directly into the kidney interstitium to mimic endogenous prostaglandin E2 production by renal cells. The maximum change in each of these parameters occurred when 10(-5) M PGE2 was infused. Renal blood flow increased from 4.70 +/- 0.91 to 5.45 +/- 0.35 ml/min (p less than 0.05) while renal interstitial hydrostatic pressure decreased from 3.9 +/- 0.4 to 2.6 +/- 0.5 mmHg (p less than 0.05) and fractional excretion of sodium decreased from 1.02 +/- 0.20 to 0.61 +/- 0.12% (p less than 0.05). Thus, the present study demonstrates that renal interstitial infusion of prostaglandin E2 increases total renal blood flow but decreases both renal interstitial hydrostatic pressure and urinary sodium excretion in the rat.     

Effects of synthetic atrial natriuretic factor (ANF) on renin-aldosterone axis in the conscious newborn calf

The effects of synthetic atrial natriuretic factor (ANF) on the renin-aldosterone axis were studied in fifteen 4-7 day-old male milk-fed calves divided into 3 groups of 5 animals each. Synthetic ANF intravenous (i.v.) administration (1.6 micrograms/kg body wt over 30 min) induced a transient significant fall in plasma renin activity (from 2.5 +/- 0.3 to 1.7 +/- 0.3 ng angiotensin l/ml/h; P less than 0.05) but failed to reduce basal plasma aldosterone levels in the first group of animals. Administration (i.v.) of angiotensin II (AII) (0.8 micrograms/kg body wt for 75 min) was accompanied by a progressive fall in plasma renin activity (from 2.2 +/- 0.3 to 0.8 +/- 0.1 ng angiotensin l/ml/h; P less than 0.01) and by an increase in plasma aldosterone levels (from 55 +/- 3 to 86 +/- 5 pg/ml; P less than 0.01) both in the second and the third groups; addition of ANF to AII infusion (AII: 0.5 mu/kg body wt for 45 min; AII: 0.3 micrograms/kg body wt and ANF 1.6 micrograms/kg body wt during 30 min) in the third group did not modify plasma renin activity or AII-stimulated plasma aldosterone levels when compared to the AII-treated group. These findings show that in the newborn calf ANF is able to reduce plasma renin activity but fails to affect basal and AII-stimulated plasma aldosterone levels, suggesting that the zona glomerulosa of the newborn adrenal cortex is insensitive to a diuretic, natriuretic and hypotensive dose of the atrial peptide.     

Cardiovascular and renal effects of calcitonin gene-related peptide in hypertensive dogs

The systemic cardiovascular and renal effects of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in conscious normotensive and one-kidney one-clip (1K-1C) hypertensive dogs. beta-hCGRP was infused intravenously at 10 and 50 ng/kg/min for 75-min periods each. Mean arterial pressure did not change significantly (p greater than 0.05) in either group during low dose infusion of beta-hCGRP, but infusion of beta-hCGRP at 50 ng/kg/min produced a fall in mean arterial pressure from 140 +/- 4 to 116 +/- 6 mmHg (p less than 0.05) in the hypertensive dogs (n = 4) and from 100 +/- 4 to 78 +/- 3 mmHg (p less than 0.05) in the normotensive dogs (n = 4). Heart rates increased significantly during infusion of beta-hCGRP in both groups. Also, renal sodium and potassium excretion decreased (p less than 0.05) in the two groups at both the low and high doses of beta-hCGRP. Creatinine clearance was unchanged in normal dogs and decreased (p less than 0.05) in 1K-1C hypertensive dogs at the high rate of beta-hCGRP infusion. The clearance of p-aminohippurate increased approximately 20% (p less than 0.05) in both groups with the low dose infusion of beta-hCGRP but further increases were elicited only in the normotensive dogs in response to the elevation in the beta-hCGRP infusion rate. Plasma renin and aldosterone levels increased (p less than 0.05) above control levels during the maximum hypotensive response to beta-hCGRP infusion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Load as an acute determinant of end-diastolic pressure-volume relation

Afterload-induced changes in myocardial relaxation are a mechanism for diastolic dysfunction when afterload is elevated beyond certain limits. The present study investigated the effects of acute afterload and preload changes on the position of the end-diastolic (ED) pressure-volume (P-V) relation. Beat-to-beat afterload elevations were induced in seven open-chest rabbits by gradually occluding the ascending aorta to increase peak left ventricular pressure (LVP) from baseline to isovolumetric level. Afterload elevations were performed at three ED LVP: 2.0 +/- 0.2 (low), 5.7 +/- 0.2 (mid), and 9.6 +/- 0.6 (high) mmHg. Preload was altered with caval occlusions and/or intravenous dextran. Afterload elevations induced an upward shift of the diastolic P-V relation, which became more important as afterload and/or preload increased. For instance, maximal afterload elevations shifted this relation upward 2.2 +/- 0. 5, 5.1 +/- 0.8, and 12.1 +/- 1.7 mmHg at low, mid, and high preload, respectively. These effects were partially due to changes in relaxation rate and time available to relax. In conclusion, load is an acute determinant of the ED P-V relation, which, therefore, does not provide a load-independent assessment of diastolic function.     

Specific desensitization of the canine renal vasculature to angiotensin II despite cyclo-oxygenase inhibition

Intrarenal angiotensin (AII) infusion results in a poorly sustained renal vasoconstrictor response. To examine the relationship between fade and renal tachyphylaxis to AII, sub-pressor doses of AII and norepinephrine (NE) were injected into the renal arteries of anesthetized dogs, resulting in a transient reduction (greater than 50 percent) in renal blood flow. Continuous intrarenal AII infusion, sufficient to reduce renal blood flow by 50 percent, followed. Within five minutes, despite continued AII infusion, substantial recovery (73 +/- 11 percent) of renal blood flow occurred; however, the response to AII bolus injection was lost, but that to NE was sustained. A second group of dogs received indomethacin (5 mg/kg intravenously) 30 minutes prior to the study; the reduction in renal blood flow was better sustained; however, renal tachyphylaxis was still evident.     

Action of atrial natriuretic peptide and angiotensin II on the myocardium: studies in isolated rat ventricular cardiomyocytes

Isolated calcium-tolerant rat ventricular cardiomyocytes were used to characterize the effects of atrial natriuretic peptide (ANP), Angiotensin II (AII) and their interaction on the myocardial contraction-/relaxation pattern free of interference from other types of cardiac cells. Binding of 125I-ANP showed a KD of 12 pM and approximately 600 binding sites per cell. At 37 degrees C (rate 140 bpm) ANP decreased the contraction maximum with an EC50 of about 70 pM, maximal decrease was 35%. ANP (10(-7) M) raised cellular cyclic-GMP from 0.76+/-0.12 to 1.32+/-0.13 pmole/10(6) cells (73%, p less than 0.05). Angiotensin II increased contractility by a maximum of 32% at 10(-7) M; the EC50 was 8 x 10(-10) M. AII markedly delayed relaxation (reduction of maximum relaxation velocity from 0.092 to 0.063 mm/s; p less than 0.05). ANP (10(-7) M) increased the effect of AII (10(-8) M) on contractility by 66% without changing relaxation parameters significantly. This unexpected interaction may be relevant in pathological conditions where both AII and ANP are stimulated, such as heart failure or secondary hypertension.     

Early mitral deceleration and left atrial stiffness

Left ventricular (LV) filling deceleration time (DT) is determined by the sum of atrial and ventricular stiffnesses (KLA + KLV). If KLA, however, is close to zero, then DT would reflect KLV only. The purpose of this study was to quantify KLA during DT. In 15 patients, KLV was assessed, immediately after cardiopulmonary bypass, from E wave DT as derived from mitral tracings obtained by transesophageal echocardiography and computed according to a validated formula. In each patient, a left atrial (LA) volume curve was also obtained combining mitral and pulmonary vein (PV) cumulative flow plus LA volume measured at end diastole. Time-adjusted LA pressure was measured simultaneously with Doppler data in all patients. KLA was then calculated during the ascending limb of the V loop and during DT. LA volume decreased by 7.3 +/- 6.5 ml/m2 during the first of mitral DT, whereas LV volume increased 9.4 +/- 8.4 ml/m2 (both P < 0.001). There was a small amount of blood coming from the PV during the same time interval, with the cumulative flow averaging 3.2 +/- 2.4 ml/m(2) (P < 0.001). Mean LA pressure was 10.0 +/- 5.1 mmHg, and it did not change during DT [from 7.8 +/- 4.3 to 8.0 +/- 4.3 mmHg, not significant (NS)], making KLA, which averaged 0.46 +/- 0.39 mmHg/ml during the V loop, close to zero during DT [KLA(DT): from -0.002 +/- 0.08 to -0.001 +/- 0.031 mmHg/ml, NS]. KLV, as assessed noninvasively from DT, averaged 0.25 +/- 0.32 mmHg/ml. In conclusion, notwithstanding the significant decrement in LA volume, KLA does not change and can be considered not different from zero during DT. Thus KLA does not affect the estimation of KLV from Doppler parameters.     

Effects of prostaglandin E1 on microvascular haemodynamics in progressive systemic sclerosis.

The effects of prostaglandin E1 infusion on nailfold capillary haemodynamics were studied in eight patients with Raynaud''s phenomenon secondary to progressive systemic sclerosis. Using a modified Landis microinjection technique the mean (+/- SEM) transcapillary pressure gradient was increased during and six weeks after infusion by 13.9 +/- 3.2 cm H2O (p less than 0.05) and 5.5 +/- 2.5 cm H2O (p less than 0.05) respectively. Capillary red cell velocity measured in two patients by video television microscopy also increased during and after infusion with prostaglandin E1. Six patients claimed subjective benefit and in three their ulcers healed. These findings support the observed beneficial effect of prostaglandin E1 and suggest that it improves the nutritive capillary circulation by lowering precapillary resistance.     

Mechanisms mediating canine renal vasoconstriction induced by nicotine infusion

We investigated the respective contributions of the renin-angiotensin and alpha-adrenergic systems to nicotine-induced, canine, renal vasoconstriction by using saralasin (4 micrograms/kg/min) and phentolamine (25 micrograms/kg/min) blockade respectively. Nicotine infusion (0.024 mg/kg/min) increased mean arterial blood pressure (MABP) (114 +/- 3.0 to 219 +/- 8.0 mmHg) and decreased total renal blood flow (TRBF) (3.12 +/- 0.34 to 1.60 +/- 0.37 ml/min/g). Nicotine infusion produced a significantly lesser blood flow in outer cortex (OC), inner cortex (IC), and outer medulla (OM) compared to control dogs. The intrarenal-artery infusion of saralasin or phentolamine had no effect on the nicotine-induced MABP changes. Phentolamine infusion prior to nicotine resulted in a significantly greater TRBF (P less than 0.01), OC (p less than 0.001), IC (p less than 0.001) and OM (p less than 0.01) flow than in the group that received nicotine only. Saralasin pretreatment prior to nicotine resulted only in a significantly (p less than 0.01) greater OC flow than nicotine only. Our data suggest that while angiotensin II mediates a portion of the action of nicotine on the OC renal vasculature, the alpha adrenergic system predominates as the mediator of nicotine-induced renal vasoconstriction in the first 7 minutes of nicotine infusion.     

Effect of increased afterload on right ventricular function in newborn pigs

The effect of a progressive increase in right ventricular (RV) afterload was studied in pigs less than 24 h (group I) and 3-5 days old (group III). RV load was applied to increase mean pulmonary arterial pressure (Ppa) until right to left shunt was observed. Initially, pigs in group I had a significantly lower systemic arterial pressure (Psa = 63 +/- 2 vs. 82 +/- 5 mmHg) and higher Ppa (30 +/- 1 vs. 23 +/- 2 mmHg) even though the RV stroke work (RVSW) was similar (54.3 +/- 10.8 vs. 32.4 +/- 2.1 mmHg/ml) to group II. After a progressive rise in afterload, pigs in group I could maintain a higher RV stroke volume than those in group II (1.3 +/- 0.3 vs. 0.4 +/- 0.1 ml; P less than 0.05). At shunt condition, the RVSW was increased by 21 +/- 14% of the initial value in group I vs. a 32 +/- 8% decrease in group II (P less than 0.05). The ductus arteriosus was constricted and right-to-left shunt was observed in all animals at the foramen ovale level even though Ppa exceeded Psa before the rise in the right atrial pressure in group I. Thus, as RV afterload is increased in the pig, the older animals' right ventricle is progressively less capable of maintaining pulmonary blood flow than animals within 24 h of birth.     

Angiotensin II mediates hyperadrenergic activity evoked by sodium restriction in essential hypertension

We examined the possible involvement of angiotensin II in the modulation of circulating norepinephrine produced by acute sodium restriction in essential hypertensive patients (n = 18). Sodium restriction potentiated plasma level of norepinephrine in parallel with an increased plasma renin activity (r = 0.81, F = 31.2, p less than 0.05 given by the percent changes). An intravenous infusion of sarcosine-1, isoleucine-8 angiotensin II produced a significant fall in mean arterial pressure (-6 +/- 2 mmHg, p less than 0.05) in patients on sodium restriction but not before sodium restriction, while the infusion of the antagonist produced a greater decrease (p less than 0.05) in plasma norepinephrine with sodium restriction (-158 +/- 23 pg/ml, p less than 0.05) when compared to that obtained before sodium restriction (-91 +/- 11 pg/ml, p less than 0.05). A single oral administration of an angiotensin I converting enzyme inhibitor, captopril caused a greater fall (p less than 0.01) in mean arterial pressure after sodium restriction (-32 +/- 3 mmHg, p less than 0.05) compared to that given before (-21 +/- 3 mmHg, p less than 0.05). However, sodium restriction did not affect the magnitude of reflex increase in plasma norepinephrine to hypotension evoked by captopril (from +88 +/- 16 pg/ml to +87 +/- 17 pg/ml; p greater than 0.05). It can be interpreted that acute sodium depletion results in a substantial contribution of angiotensin II to the expression of hyperadrenergic activity.     

Haemodynamic effects of angiotensin II in conscious, non-ascitic cirrhotic rats

The effect of angiotensin II (AII) on systemic and regional haemodynamics was studied in 18 control and 18 cirrhotic, non-ascitic conscious rats (CCl4/phenobarbital model). Cirrhotic rats were found to retain sodium and to have normal plasma renin and plasma aldosterone concentrations when compared with control animals. Cirrhotic rats showed an enhanced cardiac output (34.4 +/- 0.5 vs. 27.5 +/- 2.0 ml/min in controls) and decreased peripheral resistances (2.96 +/- 0.25 vs. 3.95 +/- 0.31 mm Hg/min/100 g/ml in controls) under basal conditions. When AII was administered cardiac output decreased by 10.7 +/- 1.2% in cirrhotic rats, whereas it increased in control animals (11.2 +/- 2%, p less than 0.005). The AII-induced increase in arterial pressure was lower in cirrhotic than in control rats. The renal blood supply was particularly impaired by AII in cirrhotics, with a maintained flow to other organs (muscle, testes). It is concluded that the response to AII is disturbed in rats with hepatic cirrhosis even in a stage without ascites and with plasma renin and aldosterone concentrations similar to those of control animals.     

Recovery from heart failure: structural and functional analysis in a canine model

Chronic, rapid ventricular pacing produces congestive heart failure in the dog. Using echocardiography, the features of developing heart failure were analysed and the capacity of this model for recovery was assessed once pacing had been discontinued. Fifteen dogs were studied; nine were paced at 250 beats/min (bpm) to severe heart failure (5.0 +/- 1.8 weeks) and six served as sham controls. In the paced animals at severe heart failure, two-dimensional echocardiography demonstrated a significant increase in diastolic cross-sectional cardiac area (from 11 +/- 3 to 16 +/- 2 cm2, p less than 0.05), associated with a marked fall n area ejection fraction (54 +/- 8 to 21 +/- 8%, p less than 0.05), and significant left ventricular wall thinning (from 6.0 +/- 0.7 to 4.7 +/- 0.9 mm, p less than 0.05). In addition, significant increases in heart rate (77 +/- 7 to 126 +/- 13 bpm, sinus rhythm; p less than 0.05), respiratory rate (41 +/- 13 to 80 +/- 20 cycles/min, p less than 0.05), and body weight (21 +/- 1 to 24 +/- 3 kg, p less than 0.05) were noted. Serum sodium fell (146 +/- 3 to 140 +/- 8 mmol/L, p less than 0.05), while blood urea nitrogen (6 +/- 2 to 10 +/- 2 mmol/L, p less than 0.05) and creatinine (86 +/- 12 to 101 +/- 15 mmol/d, p less than 0.05) increased. Recovery was characterized by rapid improvement such that all measured parameters normalized by 1 week, except for cross-sectional cardiac area which remained dilated up to 4 weeks (14 +/- 3 cm2, p less than 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)