Plasmodium berghei: malaria infection causes increased cardiac output in rats, Rattus rattus

Thirty-two 4-week-old male Wistar rats were infected with Plasmodium berghei malaria. On Days 12 through 14, blood volume, arterial blood pressure, right ventricular pressure, heart rate, cardiac output, stroke volume, hematocrit, and vascular resistances were determined. All of the cardiovascular parameters measured, with the exception of calculated pulmonary vascular resistance, changed progressively as the peripheral blood parasitemia increased. With a rising parasitemia, cardiac output increased, despite a reduced heart rate. The highest parasitemia of 63% was accompanied by a doubling of the normal cardiac output. The relationship between parasitemia and cardiac output can be described by the equation, cardiac output = (6.14) x % parasitemia + 452 ml/min/kg. The mean arterial blood pressure was lower than controls when parasitemia exceeded 20%, whereas systolic right ventricular pressure was elevated only at the highest parasitemias. When noninfected control rats were compared with those animals having parasitemias greater than 40%, in the infected animals, mean arterial pressure was 28% lower (P less than 0.01) and systolic right ventricular pressure rose by 21% (P less than 0.02). A 50% decline was observed in the total peripheral vascular resistance (P less than 0.01), although the pulmonary resistance was apparently unchanged. With P. berghei infection, there is also a marked anemia, an increase in plasma volume, and a 16% increase in blood volume (% body weight). It is concluded from these results that although the hemodynamic changes previously reported in the literature indicate that infection with malaria may result in focal blockages in microvessels and poor tissue perfusion, the total systemic effect, in the rat, is an increase in cardiac output secondary to a reduced peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Venous hemodynamic responses to acute temperature increase in the rainbow trout (Oncorhynchus mykiss)

Many ectotherms regularly experience considerable short-term variations in environmental temperature, which affects their body temperature. Here we investigate the cardiovascular responses to a stepwise acute temperature increase from 10 to 13 and 16 degrees C in rainbow trout (Oncorhynchus mykiss). Cardiac output increased by 20 and 31% at 13 and 16 degrees C, respectively. This increase was entirely mediated by an increased heart rate (fH), whereas stroke volume (SV) decreased significantly by 20% at 16 degrees C. The mean circulatory filling pressure (MCFP), a measure of venous capacitance, increased with temperature. Central venous pressure (Pven) did not change, whereas the pressure gradient for venous return (MCFP-Pven) was significantly increased at both 13 and 16 degrees C. Blood volume, as measured by the dilution of 51Cr-labeled red blood cells, was temperature insensitive in both intact and splenectomized trout. This study demonstrates that venous capacitance in trout decreases, but cardiac filling pressure as estimated by Pven does not change when cardiac output increases during an acute temperature increase. SV was compromised as fH increased with temperature. The decreased capacitance likely serves to prevent passive pooling of blood in the venous periphery and to maintain cardiac filling pressure and a favorable pressure gradient for venous return.     

Endothelin induces an initial increase in cardiac output associated with selective vasodilation in rats

The systemic and regional hemodynamic effects of endothelin (ET), a novel endothelial derived vasoconstrictor peptide were studied in Wistar Kyoto rats. A bolus of 1 nmol/Kg ET intravenously induced a transient 43% decrease in blood pressure associated with a 57% decrease in systemic resistance and a 30% increase in cardiac output (p less than 0.01 for all parameters). This was followed by an increase of 20% in arterial pressure and of 71% in systemic resistance and a decrease of 30% in cardiac output at 10 minutes. The initial fall in blood pressure was not abolished by pretreatment with verapamil, captopril, indomethacin, ketanserin, atropine, methylene blue or ethanol. Verapamil abolished the hypertensive phase by markedly decreasing cardiac output. ET had selective effects on the arterial tree; during the hypotensive phase it caused a transient increase in blood flow in the carotid and femoral arteries (+41% and +83% respectively, p less than 0.01) but a decrease in flow in the renal and mesenteric arteries (-53% and -44% respectively, p less than 0.05). Accordingly, there was a decrease in resistance in the carotid and femoral beds (-55% and -67% respectively, p less than 0.01) and an increase in resistance in the renal and mesenteric beds (+102%; p less than 0.01 and +23%; p = N.S. respectively). Subsequently there was an increase in resistance in all vascular beds to variable degrees. The maximal increase in resistance was in the renal bed (+156%). Thus, ET causes initially a potent systemic vasorelaxation and an increase in cardiac output later progressing to systemic vasoconstriction and a decrease in cardiac output. The initial vasodilation is selective, appearing in musculocutaneous beds but not in visceral beds.     

Cardiovascular effects of centrally administered endothelin-1 and its relationship to changes in cerebral blood flow

Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng, i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (−40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (−46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 μg, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET_A receptors.     

Effect of volume expansion on hemodynamic variables in nephrectomized dogs

We have previously demonstrated that blood pressure elevation by acute blood volume expansion is volume-dependent during the infusion period and resistance-dependent in the post-infusion period in normal anesthetized dogs, and that such an increase in blood pressure is associated with a potentiation of the pressor response to norepinephrine. To evaluate the possible renal contribution to these hemodynamic changes, blood volume expansion was performed for 1 h with dextran dissolved in lactated Ringer's solution (20 ml/kg) in 15 nephrectomized dogs. The mean blood pressure, cardiac output and total peripheral resistance at the end of infusion were 126%, 225% and 60%, respectively; 3 h after volume expansion they were 126%, 151%, and 92% respectively. However, in 4 dogs, there was an increase in mean blood pressure (138%) 3 h after volume expansion. This was thought to result from an increase in the total peripheral resistance (133%) associated with the recovery of cardiac output (106%). The pressor response to norepinephrine (0.5 microgram/kg) was potentiated after volume expansion. These results indicate that the handling of volume by the kidney contributed to the maintenance of an elevated level of cardiac output. However, nephrectomy did not seem to interfere with the hemodynamic switching of the causative factor for blood pressure elevation from increased cardiac output to increased total peripheral resistance. Neither was the potentiation of pressor response to norepinephrine affected.     

Right atrial dimension-pressure relation during volume expansion is unaltered by pregnancy in the rat

Blood volume expands significantly during pregnancy, but afferent signals from cardiac receptors are reduced. In addition, during exogenous volume expansion, right atrial pressure (RAP) increases more for equivalent volumes in pregnant animals, implying reduced atrial compliance. To examine possible gestational alterations in atrial dimension during volume expansion, we compared the effects of volume expansion on RAP and right atrial dimension (RAD) in pregnant vs. virgin rats. Anesthetized animals were ventilated and catheterized for measurement of arterial pressure and RAP and for drug infusion. Through a parasternal incision, ultrasonic crystals were glued to the medial and lateral surfaces of the right atrium for measurement of RAD. Plasma volume and hematocrit were determined before experimentation. RAP, RAD, and arterial pressure were recorded at baseline and during progressive volume expansion (6% dextran, 60% of initial blood volume). Baseline RAP was similar in the two groups: 2.82 +/- 0.40 and 2.72 +/- 0.47 mmHg in pregnant and virgin rats, respectively. Basal RAD was significantly larger in pregnant than in virgin rats: 4.36 +/- 0.66 vs. 3.36 +/- 0.48 mm. Despite increased basal RAD in pregnant rats, the slope of the RAD-RAP relation during volume expansion was similar in the two groups. Results indicate that resting RAD is increased in pregnant rats and that the change in dimension during volume loads is similar to that in virgin rats. Thus, during pregnancy, the right atrium appears to accommodate the increased blood volume, and reduced afferent signaling most likely is due to mechanisms other than mechanical alterations of the atrium by expanded volume.     

Changes in myocardial contractility and contractile proteins after four weeks of simulated [correction of simulate] weightlessness in rats

The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn, this distribution determines cardiac pump function. One of the most profound circulatory changes that occurs in man during exposure to weightlessness is a cephalad redistribution of fluid caused by the lack of hydrostatic pressure in this microgravitative environment. The cephalad redistribution of fluid results in a loss of blood volume and then induces a decrease in preload. Recently, a decrease in sensitivity of arteriole to catecholamine has reported in rats of simulated weightlessness. This change in arteriole may reduce afterload. As a result, cardiovascular system may be shifted to a hypokinetic state during weightlessness condition for long-term. Echocardiographic data from astronauts during space flight showed an increase in heart rate, a 12 % decrease in stroke volume, and a 16 % decrease in left end diastolic volume. Electron-microscopic studies have shown changes in cardiac morphology in rats after exposure to microgravity for 7-12.5 days. After the COSMOS 2044 flight for 14 days, the light-microscopic studies have shown an atrophy of papillary muscles in rats left cardiac ventricle. It is not clear whether the function of atrophic myocardium is impaired. The data in three aspects as mentioned above suggest that weightlessness or simulated weightlessness may decrease the myocardial function. However, definite changes in cardiac performance have been hard to prove due to many limits. This studies were to answer two questions: Is the myocardial contractility depressed in rats subjected to simulated weightlessness for four weeks? What are the underlying mechanisms of the changing contractility?     

Dysfunction of the myocardium related to chronic insufficiency of nigro-striatal dopamine in rats and correction of these disturbances with melatonin

We studied the dependence of the maximum and final diastolic pressures in the left ventricle on the level of tension of the myocardium (the latter parameter was measured using a dosed increase in the volume of a polyethylene cartridge inserted into the cardiac ventricle) on isolated hearts of control rats and animals with chronic nigro-striatal (NS) dopamine (DA) insufficiency induced by unilateral injection of a selective neurotoxin, 6-hydroxydopamine, into the brain (model of hemiparkinsonism). In addition, we calculated the diastolic rigidity of the myocardium (the ratio between the increment of the final diastolic pressure and the enhancement of the volume of the cartridge in the left ventricle). We found that, under conditions of insufficiency of cerebral DA, the reactivity of the myocardium with respect to an increase in the volume loading, i.e., the ability of the cardiac muscle to intensify the contraction force upon expansion of the ventricle, is disturbed. The plateau of the Frank-Starling curve in rats with DA insufficiency was significantly smaller than that observed in control animals, and the rigidity of the myocardium increased. Therefore, we demonstrated that the state of the cardiac muscle becomes worse in rats with chronic NS DA insufficiency. A single injection of a powerful antioxidant and inhibitor of opening of the mitochondrial pore, melatonin, into animals with the model of hemiparkinsonism (1 h prior to the experiment) restored significantly the disturbed contractile function of the heart. Neirofiziologiya/Neurophysiology, Vol. 40, No. 2, pp. 100–104, March–April, 2008.     

Cardiac pump function of the isolated rat heart at two modes of energy deprivation and effect of adrenergic stimulation

The contractile function of the isolated rat heart and high energy phosphate content were evaluated under conditions of depressed energy supply caused by disturbances either in mitochondrial ATP production or ATP-phosphocreatine transformation. Amytal (0.3 mM), an inhibitor of mitochondrial respiration, or iodoacetamide (IAA, 0.1 mM) reducing in this dose creatine kinase activity to 19% of the initial level, were used, respectively. Myocardial ATP content remained unaffected in both groups and PCr content decreased to 37% only in amytal-treated group. Very similar alterations in cardiac pump function during volume load were observed in both treated groups; maximal cardiac output was significantly less by 30%, cardiac pressure-volume work by 38–40%, left ventricular (LV) systolic pressure by 24–29%, and LV +dP/dt by 36–39%. In contrast, the extent of decreased LV distensibility was different, a curve relating LV filling volume and end-diastolic pressure was shifted up and to the left much more prominently after IAA treatment. Heart rate was decreased by 24% only in amytal-treated group. Results indicate that a decreased myocardial distensibility is a dominating feature in the acute cardiac pump failure caused by an inhibition of myocardial creatine kinase. Isoproterenol (0.1 M) substantially increased heart rate and pressure-rate product in IAA-treated hearts but failed to increase cardiac work probably due to its inability to improve myocardial distensibility.     

Systemic hemodynamic changes during the development of DOCA-salt hypertension. The effect of neonatal sympathectomy

The elevation of the cardiac index was discovered at the initial stage of DOCA-salt hypertension in rats. The blood pressure rise at the stage of stable hypertension was caused by an increase in the total peripheral vascular resistance. Neonatal sympathectomy prevented the development of DOCA-salt hypertension and elevation of the cardiac index revealed in control sympathectomized rats.     

Cardiovascular measurements relevant to heart size in copper-deficient rats.

Dietary copper deficiency in animals is often associated with cardiac enlargement and anemia. In this study we examined the hypothesis that anemia leads to a high cardiac output state that results in work-induced (physiological) cardiac hypertrophy. Blood pressure was measured by carotid cannulation and cardiac output was measured by aortic flow probe in anesthetized, open-chested rats that had been subjected to various degrees of dietary copper deficiency for five weeks. Cardiac output was unaffected by dietary copper deficiency. However, the components of cardiac output were found to vary reciprocally, heart rate decreasing and stroke volume increasing with copper deficiency. Further, total peripheral resistance, calculated as the ratio of mean arterial blood pressure and cardiac output, was depressed by dietary copper deficiency. These findings suggest that bradycardia and depression of vascular resistance induced by copper deficiency contribute to increased venous filling and a resultant increase in stroke volume; these factors may lead to cardiac hypertrophy. A significant correlation between stroke volume and heart weight in rats of varying copper status supports this conclusion.     

Cadmium as hypertensive agent. Effect on ion excretion in rats

1. Sodium, K and Cl excretion and changes in blood volume were studied after parenteral injection of Cd²⁺ (1 μmol/100g body weight) in intact and adrenalectomized rats.2. The final systolic arterial pressure and mean arterial pressure of adrenalectomized rats increase significantly after Cd²⁺ administration compared with values from control group and initial systolic arterial pressure of each group.3. Cadmium administration induced a significant inhibition of Na⁺ excretion in urine and a decrease in blood volume in ADX rats compared with values from control or sham operated rats.4. The possibility that hypertension induced by Cd may be explained by inhibition of Na excretion and changes in blood volume is discussed.     

The effect of hypothermia on the cardiovascular system and the pressor actions of angiotensin II

1. 1.|The effect of hypothermia (24°C) on the pressor action of angiotensin II (ANG II) was studied in anaesthetized rats.

2. 2.|Hypothermia prolonged the pressor response to ANG II leading to an increase in the estimated half-life of ANG II.

3. 3.|Hypothermia also caused a significant increase in stroke volume and a significant decrease in heart rate with no change in cardiac output.

4. 4.|It is conclued that hypothermia causes a prolongation of the pressor action of ANG II probably by reducing the activity of the catabolic enzymes leading to an increase in ANG II half-life.

Pregnancy alters hemodynamic responses to hemorrhage in conscious rabbits

Pregnant animals are less able to maintain mean arterial pressure (MAP) during hemorrhage compared with nonpregnant animals, but the hemodynamic basis of this difference is unknown. The hypothesis that pregnancy attenuates responses of cardiac output, as well as total peripheral resistance (TPR) and femoral conductance, to hemorrhage was tested in conscious rabbits in both the pregnant and nonpregnant state (n = 10). During continuous slow blood loss (2% of the initial blood volume per minute), MAP was maintained initially in both groups. However, MAP then abruptly decreased to <45 mmHg in all animals after a smaller percentage of the initial blood volume was removed in pregnant compared with nonpregnant rabbits (43.6 +/- 1.7%, nonpregnant; 29.6 +/- 2.2%, pregnant; P < 0.005). The more rapid transition to hypotension exhibited by pregnant rabbits was associated with greater initial falls in cardiac output (-56 +/- 10 ml/min, nonpregnant; -216 +/- 33 ml/min, pregnant; P < 0.005) and stroke volume (0.8 +/- 0.1 ml/beat, nonpregnant; -1.3 +/- 0.1 ml/beat, pregnant; P < 0.05). In addition, the increase in TPR as a function of the decrease in cardiac output was markedly attenuated (P < 0.0001) during pregnancy. Whereas femoral conductance decreased in nonpregnant rabbits, it did not change significantly in pregnant animals. In conclusion, the lesser ability of conscious pregnant rabbits to maintain MAP during hemorrhage is due largely to a greater decrease in cardiac output but also to inadequate reflex increases in TPR, possibly in part in the femoral vascular bed.     

Hemodynamic effects of a combination of clonidine and propranolol in conscious cirrhotic rats

The hemodynamic effects of the combination of clonidine and propranolol were studied in conscious rats with portal hypertension owing to secondary biliary cirrhosis. Pressure and blood flow measurements (radioactive microsphere method) were performed in three groups of eight rats before and after drug administration. The combined effects of clonidine (2 micrograms/100 g body wt., i.v.) and propranolol (0.2 mg/min for 10 min) were compared with those observed after administration of either clonidine alone or propranolol alone. The association of clonidine and propranolol induced significant decreases in portal pressure (30%) and portal tributary blood flow (43%), the magnitude of these changes being significantly more marked than that after administration of either clonidine alone (12 and 20%, respectively) or propranolol alone (16 and 17%, respectively). After the combination, no significant change in arterial pressure was observed, but cardiac output significantly decreased and systemic vascular resistance significantly increased. Renal blood flow decreased to a similar extent (40%) in the three groups. These findings indicate that the combination of clonidine and propranolol is more effective for reversing splanchnic hemodynamic changes than clonidine alone or propranolol alone. The additive effects of this association are in agreement with the action of clonidine and propranolol at different levels (central and peripheral) and on different receptors (alpha and beta). It suggests that an increase in sympathetic activity may play a major role in hemodynamic changes observed in experimental cirrhosis.     

The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias)

The aim of the present study was to evaluate the effects of endothelin-1-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg^-1) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O₂. The effects of endothelin-1 on arterial blood partial pressure of CO₂ were not synchronised with the changes in O₂ partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO₂ partial pressure was increased transiently by ~1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO₂ partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (~0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml^-1) eliminated the increase in CO₂ partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO₂ partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by ~10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.     

Blood volume, the venous system, preload, and cardiac output

Cardiac output is determined by heart rate, by contractility (maximum systolic elastance, Emax) and afterload, and by diastolic ventricular compliance and preload. These relationships are illustrated using the pressure-volume loop. Diastolic compliance and Emax place limits determined by the heart within which the pressure-volume loop must lie. End-diastolic and end-systolic pressures and hence the exact position of the loop within these limits are determined by the peripheral circulation. In the presence of minimal sympathetic tone, some 60% of total blood volume is hemodynamically inactive and constitutes a blood volume reserve (the unstressed volume). The remainder of the blood volume (the stressed volume) and the compliance of the venous system determine the venous pressure. This venous pressure together with venous resistance determines venous return, right atrial pressure, cardiac preload, and hence cardiac output. Venoconstriction causes conversion of unstressed volume to the stressed volume, the blood volume reserve is converted into hemodynamically active blood volume. After hemorrhage this replaces the lost stressed volume, while in other situations where total blood volume is not reduced, it allows a sustained increase in cardiac output. The major blood volume reserve is in the splanchnic bed: the liver and intestine, and in animals but not man, the spleen. A major unsolved problem is how the conversion of unstressed volume to stressed volume by venoconstriction is reflexly controlled.     

Lower limb-localized vascular phenomena explain initial orthostatic hypotension upon standing from squat

The cause(s) of initial orthostatic hypotension (transient fall in blood pressure within 15 s upon active rising) have not been established. We tested the hypothesis that this hypotension is due to local vascular phenomena in contracting leg muscles from the brief effort of standing up. Seventeen young healthy subjects (2 male and 15 female, 22.5 ± 1.0 years) performed an active rise from resting squat after a 10-s squat, a 1-min squat, or a 5-min squat. Beat-by-beat arterial blood pressure, cardiac output, heart rate, and stroke volume (Finometer finger photoplethysmography) and right common femoral artery blood flow (Doppler and Echo ultrasound) were recorded. Data are means ± SE. Quiet standing before squat represented baseline. Peak increases in lower limb and total vascular conductance (ml·min(-1)·mmHg(-1)) upon standing were not different within squat conditions (10-s squat, 50.0 ± 12.4 vs. 44.3 ± 5.0; 1-min squat, 54.7 ± 9.2 vs. 50.5 ± 4.5; 5-min squat, 67.4 ± 13.7 vs. 58.8 ± 3.9; all P > 0.574). Mean arterial blood pressure (in mmHg) fell to a nadir well below standing baseline in all conditions despite increases in cardiac output. The hypotension predicted by the increase in leg vascular conductance accounted for this hypotension [observed vs. predicted (in mmHg): 10-s squat, -17.1 ± 2.1 vs. -18.3 ± 5.5; 1-min squat, -22.0 ± 3.8 vs. -25.3 ± 4.9; 5-min squat, -28.3 ± 4.0 vs. -29.2 ± 6.7]. We conclude that rapid contraction induced dilation in leg muscles with the effort of standing, along with a minor potential contribution of elevated lower limb arterio-venous pressure gradient, outstrips compensatory cardiac output responses and is the cause of initial orthostatic hypotension upon standing from squat.     

New insights into the pathological role of TNF-alpha in early cardiac dysfunction and subsequent heart failure after infarction in rats

A marked increase in plasma TNF-alpha has been described in patients with chronic heart failure (CHF). Nevertheless, little is known about the direct role of this cytokine early after myocardial infarction (MI) and its possible effects on the subsequent development of CHF. Wistar rats were subjected to permanent in vivo coronary artery ligation. At 5, 7, and 9 days after MI, cardiac function, passive compliance of the left ventricle (LV), and cardiac geometry were evaluated. The same model was used to perform pharmacological studies 7 days and 10 wk after MI in rats treated with monomeric recombinant human soluble TNF-alpha receptor type II (sTNF-RII, 40 microg/kg iv) or a placebo on day 3. Maximal alterations of cardiac function and geometry occurred 7 days after MI, which correlated chronologically with a peak of cardiac and serum TNF-alpha, as shown by immunohistochemistry and ELISA, respectively. sTNF-RII improved LV end-diastolic pressure under basal conditions and after volume overload 7 days and 10 wk after MI. Moreover, a significant leftward shift of the pressure-volume curve in the sTNF-RII-treated group 7 days after MI indicated a preservation of LV volume. Infarct expansion index was also significantly improved by sTNF-RII 7 days after MI (P < 0.01). Nevertheless, 10 wk after MI, geometric indexes and passive pressure-volume curves were not significantly improved by the treatment. In conclusion, TNF-alpha plays a major role in cardiac alterations 7 days after MI in rats and contributes to hemodynamic derangement, but not to cardiac remodeling, in subsequent CHF.