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Left atrial abnormalities indicating diastolic ventricular dysfunction in cardiopathy of obesity.

Electrocardiograms and M-mode echocardiograms were evaluated in lean and obese patients, either normotensive or hypertensive, who were paired for mean arterial pressure, age, and sex. Electrocardiographic evidence of left atrial abnormalities (LAA) occurred more frequently (p less than 0.01) and left atrial size was greater in the obese than in the lean patients (p less than 0.01). The left atrial emptying index, an indicator of early diastolic ventricular function, was reduced in obese patients (p less than 0.01), most markedly in those with obesity-hypertension. The left atrial emptying index was reduced in obese patients with electrocardiographic LAA compared to obese patients without this electrocardiographic sign (p less than 0.02). A close correlation (r = 0.61, p less than 0.001) was obtained between the left atrial emptying index and atrial ECG abnormalities. These left atrial abnormalities in obesity and particularly in obesity-hypertension indicate diastolic ventricular dysfunction.

Adult↗

Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.

Acromegaly↗

Acute changes in spontaneous echo contrast and atrial function after cardioversion of persistent atrial flutter.

With use of transesophageal echocardiography, the short-term effects of transthoracic electrical cardioversion of atrial flutter (AFI) on atrial mechanical function and spontaneous echo contrast were determined. Thirty patients who had AFI for a mean of 6.4 +/- 12.2 months underwent transthoracic cardioversion. A transesophageal echocardiogram was recorded immediately before cardioversion, and left atrial appendage emptying velocity and spontaneous contrast were assessed serially at 1, 3, and 5 minutes after cardioversion in 28 patients, and also at 8, 10, and 15 minutes after cardioversion in a subgroup of 13 patients. Cardioversion was deferred in 2 patients (7%) because a thrombus was found in the left atrial appendage. Before cardioversion, spontaneous contrast was present in the left atrium in 7 of 28 patients (25%) who underwent cardioversion. The mean left atrial appendage emptying velocity of 54 +/- 22 cm/s before cardioversion fell by 26% to 40 +/- 25 cm/s at 1 minute after restoration of sinus rhythm (p <0.01). There were no significant changes in the mean left atrial appendage-emptying velocity between 1 and 15 minutes after cardioversion. Within 5 minutes after conversion to sinus rhythm, left atrial spontaneous echo contrast developed de novo or worsened in 12 of the 28 patients (43%). In conclusion, the results of this study demonstrate that persistent AFI may be associated with left atrial thrombi before cardioversion and that cardioversion of AFI is associated with a significant degree of atrial stunning and formation of spontaneous echo contrast.

Adult↗

Evolution of expression of cardiac phenotypes over a 4-year period in the beta-myosin heavy chain-Q403 transgenic rabbit model of human hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by a diverse array of cardiac phenotypes evolving over several decades. We have developed transgenic rabbits that fully recapitulate the phenotype of human HCM and provide for the opportunity to delineate the sequence of evolution of cardiac phenotypes, and thus, the pathogenesis of HCM. We determined evolution of biochemical, molecular, histological, structural and functional phenotypes at 4 age-periods in 47 beta-myosin heavy chain-glutamine (MyHC-Q)-403 transgenic rabbits. Ca(+2) sensitivity of myofibrillar ATPase activity was reduced very early and in the absence of other discernible phenotypes. Myocyte disarray also occurred early, prior to, and independent of hypertrophy and fibrosis. The latter phenotypes evolved predominantly during puberty in conjunction with activation of stress-related signaling kinases. Myocardial contraction and relaxation velocities were decreased early despite normal global cardiac function and in the absence of histological phenotype. Global cardiac function declined with aging, while left atrial size was increased along with Doppler indices of left ventricular filling pressure. Thus, Ca(+2) sensitivity of myofibrillar ATPase activity is a primary phenotype expressed early and independent of the ensuing phenotypes. Pathogenesis of myocyte disarray, which exhibits age-independent penetrance, differs from those of hypertrophy and fibrosis, which show age-dependent expression. Myocardial dysfunction is an early marker that predicts subsequent development of hypertrophy. These findings in an animal model that recapitulates the phenotype of human HCM, implicate involvement of multiple independent mechanisms in the pathogenesis of cardiac phenotypes in HCM.

Adenosine Triphosphatases↗

Acute fulminant myocarditis in children and adolescents: the role of mechanical circulatory assist.

We report children and adolescents in fulminant myocarditis undergoing prolonged circulatory support with different assist devices. Between 1994 and 2004, seven children and adolescents (aged 7-18 years, mean age 13.5 years) were treated with VADs (5 Thoratec, 1 Medos, 1 Novacor) for circulatory support. Three patients underwent left ventricular support; biventricular support was necessary in four patients. Four patients (three left VADs, one bi-VAD) could be successfully bridged to heart transplantation after a mean support time of 163 days (56-258 days). One 7-year-old girl (Medos-BVAD) died after a support time of 11 days because of irreversible multiorgan failure. One 18-year-old patient was successfully weaned from Thoratec BVAD after 66 days with complete recovery of left ventricular function. As good markers, atrial and brain natriuretic peptides were found which reached normal values after recovery of myocardial function. A 15-year-old girl is still on the device. In children or adolescents with irreversible shock in fulminant myocarditis with an anticipated mortality of 100%, both successful bridging to heart transplantation and successful bridging to recovery are possible. Young patients with fulminant myocarditis should be rapidly transferred to a clinic with a mechanical circulatory support program to offer this life-saving option.

Acute Disease↗

Influence of frusemide on dynamic cardiac variables during exercise.

Exercising horses have extremely high right and left atrial pressures. Limitation in ventricular function (i.e. relaxation) may play a role in these high pressures. We studied relaxation characteristics of the right ventricular myocardium and the impact of frusemide (2.0 mg/kg bwt i.v.) on these characteristics in horses exercising at 8, 10, 12 and 14 m/s. Exercise tests were performed 4 h after administration of frusemide. Right ventricular (RV) pressure was analysed using Fast Fourier Transform techniques to remove non cardiac components of the pressure signal. Mean right atrial (RA) pressure increased with exercise and was significantly attenuated at all speeds by frusemide. RV maximum and minimum rates of pressure change with respect to time (RV + dP/dtmax, RV-dP/dtmax) increased with exercise and RV relaxation time constant (RV tau) and time of RV relaxation from 65-20% of the difference between maximum and minimum ventricular pressure (delta 65-20) decreased with exercise. Frusemide produced no significant differences in +dP/dtmax, -dP/dtmax, RV tau or delta 65-20 except at 12 m/s where RV tau was longer after frusemide (23.4 ms for frusemide vs. 19.7 ms for control). Significant reductions in stroke volume were seen at 8, 10 and 14 m/s after frusemide. These results suggest that the reduction of atrial pressure by frusemide is not due to changes in ventricular relaxation rate.

Animals↗

Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy: long term follow up of the first series of 25 patients.

OBJECTIVE: To determine the long term outcome in patients treated with percutaneous transluminal septal myocardial ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM). DESIGN AND SETTING: Observational, single centre study. PATIENTS: 25 patients (13 women, 12 men, mean (SD) age 54.7 (15.0) years) with drug treatment resistant New York Heart Association (NYHA) class 2.8 (0. 6) symptoms attributed to a high left ventricular outflow gradient (LVOTG) and a coronary artery anatomy suitable for intervention. INTERVENTION: PTSMA by injection of 4.1 (2.6) ml of alcohol (96%) into 1.4 (0.6) septal perforator arteries to ablate the hypertrophied interventricular septum. OUTCOME MEASURES: During in-hospital follow up, enzyme rise, the frequency of atrioventricular conduction lesions requiring permanent DDD pacing, and in-hospital mortality were assessed. Long term follow up (30 (4) months, range 24-36 months) included symptoms, echocardiographic measurements of left atrial and left ventricular dimensions and function, and LVOTG. RESULTS: Mean postinterventional creatine kinase rise was 780 (436) U/l. During PTSMA 13 patents developed total heart block, permanent pacing being necessary in five of them. One 86 year old patient died from ventricular fibrillation associated with intensive treatment (beta mimetic and theophylline) for coexistent severe obstructive airway disease. After three months, three patients underwent re-PTSMA because of a dissatisfactory primary result, leading to LVOTG elimination in all of them. During long term follow up, LVOTG showed sustained reduction (3 (6) mm Hg at rest and 12 (19) mm Hg with provocation) associated with stable symptomatic improvement (NYHA class 1.2 (1.0)) and without significant global left ventricular dilatation. CONCLUSIONS: PTSMA is an effective non-surgical technique for reduction of symptoms and LVOTG in HOCM. Prospective, long term observations of larger populations are necessary in order to determine the definitive significance of the procedure.

Angioplasty, Balloon, Coronary↗

Pulmonary vein flow pattern in mitral incompetence, combined mitral stenosis/incompetence and after prosthetic valve replacement.

Pulmonary vein flow (PVF) pattern was studied with an electromagnetic flowmeter in 11 patients with combined mitral stenosis/incompetence (MS/MI), in 6 patients with pure mitral incompetence (MI) and in 24 patients after mitral valve replacement (MVR). ECG, left atrial and left ventricular pressures were recorded simultaneously. The anomalous flow patterns, which were recorded, reflected the left atrial events and mitral valve function. Before MVR, the major forward flow occurred in ventricular diastole. In patients with predominating MS and small/moderate MI, a small retrograde PVF (RF) occurred in early ventricular systole, while pure or combined severe MI produced a holosystolic reversal of PVF.

Adult↗

The predictive value of chronic atrial fibrillation for the short- and long-term outcome after percutaneous mitral balloon valvotomy.

BACKGROUND AND AIM OF THE STUDY: The predictive value of chronic atrial fibrillation (AF) before percutaneous mitral balloon valvotomy (PMBV) is still under discussion. The effect of the duration of chronic AF on short- or long-term results is not known. Therefore, we analyzed the predictive value of pre-procedural chronic AF and the duration of this rhythm disturbance for short- and long-term outcome after PMBV in patients with mitral valve stenosis. METHODS: A total of 140 PMBV procedures was performed in 137 patients with severe mitral stenosis. Sixty-three patients (45%) were in chronic AF; in 40 patients (63%) the AF was of more than one year duration. A successful procedure is defined as PMBV achieved without acute mitral valve replacement, and a mitral valve area after PMBV of > or =1.5 cm2. RESULTS: Patients in chronic AF were significantly older, had a larger left atrial diameter and higher NYHA functional class, compared with patients in sinus rhythm (SR). The success rates of PMBV were 80.5% and 77.6% in patients with SR and AF, respectively (p = NS). Mean follow up was 4.2+/-2.6 years (n = 127). At four years' follow up the event-free survival was 86.5% in patients with SR, and 78.5% in those with chronic AF at baseline (p = 0.031). Multivariate analysis of the entire study population showed the presence of chronic AF to be the only pre-procedural independent predictor for severe mitral regurgitation after PMBV (p = 0.030), as well for an event (p = 0.039) and restenosis (p = 0.034) during follow up. The risk for an event or restenosis during follow up increased seven-fold when chronic AF at baseline was present for more than one year (p = 0.010). CONCLUSION: Pre-procedural chronic AF is an independent predictor for unfavorable outcome at short- and long-term follow up after PMBV. A longer duration of AF further increases the risk of an event or restenosis.

Adult↗

[Hypoxic therapy of arterial hypertension in patients with different variability of arterial pressure].

Sixty two patients with essential hypertension stage II were divided into two groups. 32 patients of group 1 received combined therapy including a course of inhalations of gas hypoxic mixture containing 10% oxygen and conventional medication (ACE inhibitors, beta-blockers, calcium antagonists, diuretics). 30 patients of group 2 (controls) were given medication alone. 24-h monitoring of arterial pressure (AP) and echocardiography suggested that high AP variability (APV) in hypertensive subjects leads to more significant changes in left ventricular and atrial structure and function typical for hypertensive heart. In high VAP, its night values are subnormal while daytime values are high in patients on combined medication and hypoxic therapy. The patients on standard medication had significantly low VAP at night while their daytime VAP tended to decrease. VAP positively correlated with hypertensive load. In high VAP hypoxic and drug therapies are less effective.

Adrenergic beta-Antagonists↗

[Clinical features and prognosis of paroxysmal atrial fibrillation in the elderly].

Eighty one elderly patients with paroxysmal atrial fibrillation were studied with respect to clinical features, effect of antiarrhythmic drugs and prognosis. 35 (43.2%) patients were associated with coronary artery disease and/or hypertension, while 23 (28.4%) patients had no other cardiovascular diseases. The latter condition was significantly less in patients over 60 years old when they had the first paroxysmal attack. Atrial fibrillation became permanent in 18 (22.2%) patients. Left atrial enlargement and abnormal cardiac function were significant independent factors affecting the type of atrial fibrillation. During an observation period of 12-84 months, the incidence of cerebral embolism and cardiac death were 6.1% and 4.9% respectively in all cases. We did not find that the prognosis of patients was affected by the types of atrial fibrillation.

Aged↗

[Treatment of junctional paroxysmal tachycardia, without patent Wolff-Parkinson-White syndrome, by sectioning an accessory Kent-His bundle].

The authors report the case of a patient suffering from a Bouveret's tachycardia without syndrome of Wolff-Parkinson-White. The analysis of the tachycardic spells however showed that during a reciprocal crisis, the circuit went through a left accessory ventriculo-atrial bundle, functioning only in the reverse direction. This accessory bundle was successfully cut by the surgeon, following the procedure of wide atrioventricular desinsertion as described by the authors of Duke University for the surgical treatment of the Wolff-Parkinson-White syndrome.

Adult↗

Fluosol cardioplegia results in complete functional recovery: a comparison with blood cardioplegia.

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Echocardiographic evaluation of left ventricular function in children with congestive cardiomyopathy.

Echocardiography was used to study left ventricular function in 37 children with congestive cardiomyopathy. Left atrial and left ventricular diameters were approximately 1.5 times that predicted by body weight, whereas systolic decrease in left ventricular diameter (shortening fraction) and increase in posterior wall thickness were half that of normal children. The ratio of left ventricular preejection period to ejection time was increased in 25 patients and normal in 10. The mean velocity of circumferential fiber shortening was decreased in 30 of 34 patients and averaged 52 percent of that predicted by heart rate. The shortening fraction was higher in the 12 patients who were asympatomatic at the time of study than in the 25 who had symptoms of congestive heart failure (19.6 +/- 2.4 standard error of the mean versus 14.6 +/- 1.2) (P less than 0.05). In 11 patients whose condition improved after therapy with digoxin and diuretic drugs, serial echocardiograms showed significant increases in shortening fraction and posterior wall thickening and decreases in left atrial diameter and the ratio of preejection period to ejection time. However, one or more indexes of left ventricular function remained abnormal, despite the resolution of symptoms and a return of heart size to normal as judged from the chest roentgenogram.

Adolescent↗

Unstable angina of crescendo pattern vs new onset: a clinical, coronary arteriographic and hemodynamic study.

Unstable angina includes a variety of clinical presentations with a different level of risk for an unfavorable outcome. In this study the authors investigated the prognostic significance of crescendo angina and new-onset angina to discuss management strategies, paying attention to the relevance of baseline clinical characteristics, coronary artery lesions, and left ventricular function, as well as their alterations during atrial pacing. Accordingly coronary arteriographic anatomy and changes in left ventricular volumes and ejection fraction before and during atrial pacing were studied by means of digital subtraction ventriculography in 18 patients with crescendo angina and in 18 patients with new-onset angina. Triple-vessel disease was more frequently observed in crescendo angina (56%; P < 0.05) as compared with the patients with new-onset angina (11%). Complex coronary morphology was statistically more likely to be found in crescendo angina. The angiographic evidence of intracoronary thrombi was found in 33% (P < 0.05) patients with crescendo angina and in 4% patients with new-onset angina. Compared with the patients with new-onset angina, patients with crescendo angina had higher end-diastolic and end-systolic volumes and lower ejection fraction at rest. At peak pacing, ejection fraction was significantly (P < 0.05) lower in crescendo angina (0.48 +/- 0.06) than in new-onset angina (0.66 +/- 0.04). In crescendo angina, during pacing, the magnitude of velocity of circumferential fiber shortening was significantly decreased as compared with new-onset angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Diastolic left ventricular function in preterm infants with a patent ductus arteriosus: a serial Doppler echocardiography study.

In very low birth weight neonates, a left-to-right shunt via persistent ductus arteriosus (PDA) may interact with diastolic left ventricular function, but specific changes of Doppler parameters have yet to be reported. In a serial transmitral Doppler study, we investigated the impact of a PDA on diastolic function parameters. Twenty-two patients with and without PDA were examined on day 3.8+/-1 and day 14+/-2 after birth. By the first examination, 13 out of 22 patients had a PDA; by the second examination, the number was still 8 out of 22. Peak early and atrial flow velocities (44.8+/-15 and 50.1+/-13 cm/s, respectively) were higher (p<0.05) for neonates with PDA compared to those with closed duct (30.9+/-6 and 34.2 cm/s, respectively). Isovolumic relaxation time (IVRT) was shorter in neonates with PDA (45+/-7 ms, N=21) compared to those with a closed duct (55.3+/-5 ms, N=23) (p<0.01). IVRT correlated inversely with cardiac index (R=-0.79, p<0.01). All observed changes reversed to the normal range after closure of the PDA. When premature infants with a PDA experience a preload challenge, early and atrial peak velocities increase and IVRT shortens significantly. This coincidence of elevated transvalvular pressure differences and decreased IVRT in neonates with immature diastolic function can best be explained as a result of left atrial pressure elevation. Consequently, pulmonary venous pressure must be elevated, with its inherent effect on pulmonary capillary physiology. Thus, the monitoring of left ventricular diastolic function adds significant information to the care of preterm infants with a PDA.

Blood Gas Analysis↗

Novel protection strategy for pulmonary transplantation.

BACKGROUND: Ischemia-reperfusion injury continues to represent a significant challenge to successful lung transplantation. Traditional pulmonary ischemic protection is performed using hypothermic hyperkalemic depolarizing solutions to reduce the metabolic demands of the ischemic organ. Measures to further reduce the effects of ischemic injury have focused on the reperfusion period. We tested the hypothesis that novel physiologic hyperpolarizing solutions-using ATP-dependent potassium channel (K(ATP)) openers-given at the induction of ischemia, will reduce cellular injury and provide superior graft function even after prolonged periods of ischemia. METHODS: An isolated blood-perfused ventilated rabbit lung model was used to study lung injury. Airway, left atrial, and pulmonary artery pressures were measured continuously during the 2-h reperfusion period. Oxygenation, as a surrogate of graft function, was measured using intermittent blood gas analysis of paired left atrial and pulmonary artery blood samples. Graft function was measured by oxygen challenge technique (F(i)O(2) = 1.0). Wet-to-dry ratio was measured at the conclusion of the 2-h reperfusion period. Control (Group I) lungs were perfused with modified Euro-Collins solution (depolarizing) and reperfused immediately (no ischemia). Traditional protection lungs were perfused with modified Euro-Collins flush solution and stored for 4 h (Group II) or 18 h (Group III) at 4 degrees C before reperfusion. Novel protection (Group IV) lungs were protected with a hyperpolarizing solution containing 100 nM Aprikalim, a specific K(ATP) channel opener, added to the modified Euro-Collins flush solution and underwent 18 h of ischemic storage at 4 degrees C before reperfusion. RESULTS: Profound graft failure was measured after 18 h of ischemic storage with traditional protection strategies (Group III). Graft function was preserved by protection with hyperpolarizing solutions even for prolonged ischemic periods (Group IV). Wet-to-dry weight ratio, airway, left atrial, and pulmonary artery pressures were not significantly different between the groups. CONCLUSIONS: We have created a model of predictable lung injury. Membrane hyperpolarization with a K(ATP) channel opener (PCO) provides superior prolonged protection from ischemia-reperfusion injury in an in vitro model of pulmonary transplantation.

Animals↗

Ringer's acetate and dextran-70 with or without hypertonic saline in endotoxin-induced shock in pigs.

The effects of Ringer's acetate, 6% dextran-70, 7.5% NaCl, and the combination of 7.5% NaCl and dextran-70 were tested in resuscitation from endotoxin shock induced by continuous iv infusion of Escherichia coli endotoxin in pigs. After about 3 h, a reproducible shock state was achieved and treatment was started, governed by the left atrial pressure. The hypertonic solutions (7.5% NaCl and 7.5% NaCl in dextran-70) did not show any overall advantages over the isotonic solutions (Ringer's acetate and dextran-70). Only transient beneficial hemodynamic effects lasting less than 30 min after infusion were seen. When dextran-70 was administered, cardiovascular function was markedly improved and oxygen delivery (DO2) and survival were significantly higher compared with the crystalloid groups (Ringer's acetate and 7.5% NaCl). Administration of large amounts of Ringer's acetate resulted in an immediate deterioration of pulmonary function. It was difficult to elevate left atrial pressure or even to keep it at baseline level, and cardiac index was only transiently increased. The overall result was a deterioration of DO2 and poor survival compared with the dextran-70 treated pigs. We conclude that dextran-70 is superior to Ringer's acetate in resuscitation from endotoxin-induced shock in pigs. Furthermore, we found no role for the use of hypertonic saline, alone or in combination with dextran, in the treatment of this type of prolonged endotoxin shock.

Animals↗